Advances in Studies on Stroke-Induced Secondary Neurodegeneration (SND) and Its Treatment

Author(s): Aishika Datta, Deepaneeta Sarmah, Kiran Kalia, Anupom Borah, Xin Wang, Kunjan R. Dave, Dileep R. Yavagal, Pallab Bhattacharya*

Journal Name: Current Topics in Medicinal Chemistry

Volume 20 , Issue 13 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: The occurrence of secondary neurodegeneration has exclusively been observed after the first incidence of stroke. In humans and rodents, post-stroke secondary neurodegeneration (SND) is an inevitable event that can lead to progressive neuronal loss at a region distant to initial infarct. SND can lead to cognitive and motor function impairment, finally causing dementia. The exact pathophysiology of the event is yet to be explored. It is seen that the thalami, in particular, are susceptible to cause SND. The reason behind this is because the thalamus functioning as the relay center and is positioned as an interlocked structure with direct synaptic signaling connection with the cortex. As SND proceeds, accumulation of misfolded proteins and microglial activation are seen in the thalamus. This leads to increased neuronal loss and worsening of functional and cognitive impairment.

Objective: There is a necessity of specific interventions to prevent post-stroke SND, which are not properly investigated to date owing to sparsely reproducible pre-clinical and clinical data. The basis of this review is to investigate about post-stroke SND and its updated treatment approaches carefully.

Methods: Our article presents a detailed survey of advances in studies on stroke-induced secondary neurodegeneration (SND) and its treatment.

Results: This article aims to put forward the pathophysiology of SND. We have also tabulated the latest treatment approaches along with different neuroimaging systems that will be helpful for future reference to explore.

Conclusion: In this article, we have reviewed the available reports on SND pathophysiology, detection techniques, and possible treatment modalities that have not been attempted to date.

Keywords: Secondary neurodegeneration, Amyloid β accumulation, Thalamic disturbances, Glial activation, Neuroinflammation, Neuro-imaging techniques.

Deldicque, L.; Francaux, M. Encyclopedia of exercise medicine in health and disease; Mooren, F.C; Ed.; Springer-Verlag Berlin: Heidelberg, 2012, pp. 145-229.
Jucker, M.; Walker, L.C. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature, 2013, 501(7465), 45-51.
[] [PMID: 24005412]
Bullmore, E.T.; Bassett, D.S. Brain graphs: graphical models of the human brain connectome. Annu. Rev. Clin. Psychol., 2011, 7, 113-140.
[] [PMID: 21128784]
Stanghellini, G.; Ballerini, M.; Presenza, S.; Mancini, M.; Northoff, G.; Cutting, J. Abnormal time experiences in major depression: an empirical qualitative study. Psychopathology, 2017, 50(2), 125-140.
[] [PMID: 27978520]
Fernández-Andújar, M.; Doornink, F.; Dacosta-Aguayo, R.; Soriano-Raya, J.J.; Miralbell, J.; Bargalló, N.; López-Cancio, E.; Pérez de la Ossa, N.; Gomis, M.; Millán, M.; Barrios, M.; Cáceres, C.; Pera, G.; Forés, R.; Clemente, I.; Dávalos, A.; Mataró, M. Remote thalamic microstructural abnormalities related to cognitive function in ischemic stroke patients. Neuropsychology, 2014, 28(6), 984-996.
[] [PMID: 24885449]
Guzik, A.; Bushnell, C. Stroke epidemiology and risk factor management. Continuum (Minneap. Minn.), 2017, 23(1), 15-39.
[PMID: 28157742]
Sarmah, D.; Kaur, H.; Saraf, J.; Pravalika, K.; Goswami, A.; Kalia, K.; Borah, A.; Wang, X.; Dave, K.R.; Yavagal, D.R.; Bhattacharya, P. Getting closer to an effective intervention of ischemic stroke: the big promise of stem cell. Transl. Stroke Res., 2018, 9(4), 356-374.
[] [PMID: 29075984]
Wanve, M.; Kaur, H.; Sarmah, D.; Saraf, J.; Pravalika, K.; Vats, K.; Kalia, K.; Borah, A.; Yavagal, D.R.; Dave, K.R.; Bhattacharya, P. Therapeutic spectrum of interferon-β in ischemic stroke. J. Neurosci. Res., 2019, 97(2), 116-127.
[] [PMID: 30320448]
Vats, K.; Sarmah, D.; Kaur, H.; Wanve, M.; Kalia, K.; Borah, A.; Dave, K.R.; Yavagal, D.R.; Bhattacharya, P. Inflammasomes in stroke: a triggering role for acid-sensing ion channels. Ann. N. Y. Acad. Sci., 2018, 1431(1), 14-24.
[] [PMID: 29917247]
Saraf, J.; Bhattacharya, P.; Kalia, K.; Borah, A.; Sarmah, D.; Kaur, H.; Dave, K.R.; Yavagal, D.R. A Friend or Foe: Calcineurin across the Gamut of Neurological Disorders. ACS Cent. Sci., 2018, 4(7), 805-819.
[] [PMID: 30062109]
Audebert, H.J.; Kukla, C.; Clarmann von Claranau, S.; Kühn, J.; Vatankhah, B.; Schenkel, J.; Ickenstein, G.W.; Haberl, R.L.; Horn, M. TEMPiS Group. Telemedicine for safe and extended use of thrombolysis in stroke: the Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria. Stroke, 2005, 36(2), 287-291.
[] [PMID: 15625294]
Sarmah, D.; Saraf, J.; Kaur, H.; Pravalika, K.; Tekade, R.K.; Borah, A.; Kalia, K.; Dave, K.R.; Bhattacharya, P. Stroke management: an emerging role of nanotechnology. Micromachines (Basel), 2017, 8(9), 262-274.
[] [PMID: 30400452]
Chen, Y.; Garcia, G.E.; Huang, W.; Constantini, S. The involvement of secondary neuronal damage in the development of neuropsychiatric disorders following brain insults. Front. Neurol., 2014, 5, 22.
[] [PMID: 24653712]
Dang, G.; Chen, X.; Chen, Y.; Zhao, Y.; Ouyang, F.; Zeng, J. Dynamic secondary degeneration in the spinal cord and ventral root after a focal cerebral infarction among hypertensive rats. Sci. Rep., 2016, 6, 22655.
[] [PMID: 26949108]
Aho, L.; Jolkkonen, J.; Alafuzoff, I. β-amyloid aggregation in human brains with cerebrovascular lesions. Stroke, 2006, 37(12), 2940-2945.
[] [PMID: 17095738]
Kim, T.; Vemuganti, R. Mechanisms of Parkinson’s disease-related proteins in mediating secondary brain damage after cerebral ischemia. J. Cereb. Blood Flow Metab., 2017, 37(6), 1910-1926.
[] [PMID: 28273718]
Zhang, J.; Chen, H.; Huang, W.; Zhou, C.; Li, J.; Xing, S.; Chen, L.; Li, C.; Dang, C.; Liu, G.; Pei, Z.; Zeng, J. Unfolded protein response is activated in the ipsilateral thalamus following focal cerebral infarction in hypertensive rats. Clin. Exp. Pharmacol. Physiol., 2016, 43(12), 1216-1224.
[] [PMID: 27558464]
Go, A.S.; Mozaffarian, D.; Roger, V.L.; Benjamin, E.J.; Berry, J.D.; Borden, W.B.; Bravata, D.M.; Dai, S.; Ford, E.S.; Fox, C.S.; Franco, S.; Fullerton, H.J.; Gillespie, C.; Hailpern, S.M.; Heit, J.A.; Howard, V.J.; Huffman, M.D.; Kissela, B.M.; Kittner, S.J.; Lackland, D.T.; Lichtman, J.H.; Lisabeth, L.D.; Magid, D.; Marcus, G.M.; Marelli, A.; Matchar, D.B.; McGuire, D.K.; Mohler, E.R.; Moy, C.S.; Mussolino, M.E.; Nichol, G.; Paynter, N.P.; Schreiner, P.J.; Sorlie, P.D.; Stein, J.; Turan, T.N.; Virani, S.S.; Wong, N.D.; Woo, D.; Turner, M.B. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation, 2009, 127, e2-e220.
Rao, G.S.; Kumar, T.V.; Rao, B.V. Determinants of consumer behaviour in India. IJEAMSAS, 2013, 1, 1-5.
Asplund, K.; Jonsson, F.; Eriksson, M.; Stegmayr, B.; Appelros, P.; Norrving, B.; Terént, A.; Åsberg, K.H. Riks-Stroke Collaboration. Patient dissatisfaction with acute stroke care. Stroke, 2009, 40(12), 3851-3856.
[] [PMID: 19850895]
Sarmah, D.; Kaur, H.; Saraf, J.; Vats, K.; Pravalika, K.; Wanve, M.; Kalia, K.; Borah, A.; Kumar, A.; Wang, X.; Yavagal, D.R.; Dave, K.R.; Bhattacharya, P. Mitochondrial dysfunction in stroke: implications of stem cell therapy. Transl. Stroke Res., 2018, 10, 121-136.
[] [PMID: 29926383]
Kluge, M.G.; Jones, K.; Kooi Ong, L.; Gowing, E.K.; Nilsson, M.; Clarkson, A.N.; Walker, F.R. Age-dependent disturbances of neuronal and glial protein expression profiles in areas of secondary neurodegeneration post-stroke. Neuroscience, 2018, 393, 185-195.
[] [PMID: 30059704]
Kluge, M.G.; Kracht, L.; Abdolhoseini, M.; Ong, L.K.; Johnson, S.J.; Nilsson, M.; Walker, F.R. Impaired microglia process dynamics post-stroke are specific to sites of secondary neurodegeneration. Glia, 2017, 65(12), 1885-1899.
[] [PMID: 28836304]
Pandian, J.D.; Sudhan, P. Stroke epidemiology and stroke care services in India. J. Stroke, 2013, 15(3), 128-134.
[] [PMID: 24396806]
Sridharan, S.E.; Unnikrishnan, J.P.; Sukumaran, S.; Sylaja, P.N.; Nayak, S.D.; Sarma, P.S.; Radhakrishnan, K. Incidence, types, risk factors, and outcome of stroke in a developing country: the Trivandrum Stroke Registry. Stroke, 2009, 40(4), 1212-1218.
[] [PMID: 19228849]
Woodruff, T.M.; Thundyil, J.; Tang, S-C.; Sobey, C.G.; Taylor, S.M.; Arumugam, T.V. Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. Mol. Neurodegener., 2011, 6(1), 11-25.
[] [PMID: 21266064]
Dirnagl, U.; Iadecola, C.; Moskowitz, M.A. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci., 1999, 22(9), 391-397.
[] [PMID: 10441299]
Chen, M.; Lu, T.J.; Chen, X.J.; Zhou, Y.; Chen, Q.; Feng, X.Y.; Xu, L.; Duan, W.H.; Xiong, Z.Q. Differential roles of NMDA receptor subtypes in ischemic neuronal cell death and ischemic tolerance. Stroke, 2008, 39(11), 3042-3048.
[] [PMID: 18688011]
Choi, D.W. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci., 1988, 11(10), 465-469.
[] [PMID: 2469166]
Chen, Z.L.; Strickland, S. Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin. Cell, 1997, 91(7), 917-925.
[] [PMID: 9428515]
Choi, D.W. Calcium: still center-stage in hypoxic-ischemic neuronal death. Trends Neurosci., 1995, 18(2), 58-60.
[] [PMID: 7537408]
Sarmah, D.; Agrawal, V.; Rane, P.; Bhute, S.; Watanabe, M.; Kalia, K.; Ghosh, Z.; Dave, K.R.; Yavagal, D.R.; Bhattacharya, P. Mesenchymal stem cell therapy in ischemic stroke: a meta-analysis of preclinical studies. Clin. Pharmacol. Ther., 2018, 103(6), 990-998.
[] [PMID: 29090465]
Zhang, J.; Zhang, Y.; Xing, S.; Liang, Z.; Zeng, J. Secondary neurodegeneration in remote regions after focal cerebral infarction: a new target for stroke management? Stroke, 2012, 43(6), 1700-1705.
[] [PMID: 22492515]
Baron, J.C.; Yamauchi, H.; Fujioka, M.; Endres, M. Selective neuronal loss in ischemic stroke and cerebrovascular disease. J. Cereb. Blood Flow Metab., 2014, 34(1), 2-18.
[] [PMID: 24192635]
Iizuka, H.; Sakatani, K.; Young, W. Neural damage in the rat thalamus after cortical infarcts. Stroke, 1990, 21(5), 790-794.
[] [PMID: 1692645]
Deschênes, M.; Veinante, P.; Zhang, Z.W. The organization of corticothalamic projections: reciprocity versus parity. Brain Res. Brain Res. Rev., 1998, 28(3), 286-308.
[] [PMID: 9858751]
Guillery, R.W.; Sherman, S.M. Thalamic relay functions and their role in corticocortical communication: generalizations from the visual system. Neuron, 2002, 33(2), 163-175.
[] [PMID: 11804565]
De Ridder, D.; Vanneste, S.; Langguth, B.; Llinas, R. Thalamocortical dysrhythmia: a theoretical update in tinnitus. Front. Neurol., 2015, 6, 124.
[] [PMID: 26106362]
Llinás, R.R.; Ribary, U.; Jeanmonod, D.; Kronberg, E.; Mitra, P.P. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc. Natl. Acad. Sci. USA, 1999, 96(26), 15222-15227.
[] [PMID: 10611366]
Llinás, R.; Urbano, F.J.; Leznik, E.; Ramírez, R.R.; van Marle, H.J.J. High-speed voltage-sensitive dye imaging. Trends Neurosci., 2005, 6, 325-333.
[PMID: 15927689]
Steriade, M. Impact of network activities on neuronal properties in corticothalamic systems. J. Neurophysiol., 2001, 86(1), 1-39.
[] [PMID: 11431485]
Sarnthein, J.; Stern, J.; Aufenberg, C.; Rousson, V.; Jeanmonod, D. Increased EEG power and slowed dominant frequency in patients with neurogenic pain. Brain, 2006, 129(Pt 1), 55-64.
[] [PMID: 16183660]
Ohara, S.; Taghva, A.; Kim, J.H.; Lenz, F.A. Spontaneous low threshold spike bursting in awake humans is different in different lateral thalamic nuclei. Exp. Brain Res., 2007, 180(2), 281-288.
[] [PMID: 17256161]
Saalmann, Y.B. Intralaminar and medial thalamic influence on cortical synchrony, information transmission and cognition. Front. Syst. Neurosci., 2014, 8, 83.
[] [PMID: 24847225]
Lambert, C.; Simon, H.; Colman, J.; Barrick, T.R. Defining thalamic nuclei and topographic connectivity gradients in vivo. Neuroimage, 2017, 158, 466-479.
[] [PMID: 27639355]
Ross, D.T.; Ebner, F.F. Thalamic retrograde degeneration following cortical injury: an excitotoxic process? Neuroscience, 1990, 35(3), 525-550.
[] [PMID: 2166245]
Johansen-Berg, H.; Behrens, T.E.J.; Sillery, E.; Ciccarelli, O.; Thompson, A.J.; Smith, S.M.; Matthews, P.M. Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus. Cereb. Cortex, 2005, 15(1), 31-39.
[] [PMID: 15238447]
Behrens, T.E.; Johansen-Berg, H.; Woolrich, M.W.; Smith, S.M.; Wheeler-Kingshott, C.A.; Boulby, P.A.; Barker, G.J.; Sillery, E.L.; Sheehan, K.; Ciccarelli, O.; Thompson, A.J.; Brady, J.M.; Matthews, P.M. Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nat. Neurosci., 2003, 6(7), 750-757.
[] [PMID: 12808459]
Kuchcinski, G.; Munsch, F.; Lopes, R.; Bigourdan, A.; Su, J.; Sagnier, S.; Renou, P.; Pruvo, J.P.; Rutt, B.K.; Dousset, V.; Sibon, I.; Tourdias, T. Thalamic alterations remote to infarct appear as focal iron accumulation and impact clinical outcome. Brain, 2017, 140(7), 1932-1946.
[] [PMID: 28549087]
Nagasawa, H.; Kogure, K. Exo-focal postischemic neuronal death in the rat brain. Brain Res., 1990, 524(2), 196-202.
[] [PMID: 2292002]
Dihné, M.; Block, F. Focal ischemia induces transient expression of IL-6 in the substantia nigra pars reticulata. Brain Res., 2001, 889(1-2), 165-173.
[] [PMID: 11166700]
Watanabe, H.; Kumon, Y.; Ohta, S.; Nakano, K.; Sakaki, S.; Matsuda, S.; Sakanaka, M. Protein synthesis inhibitor transiently reduces neuronal death in the thalamus of spontaneously hypertensive rats following cortical infarction. Neurosci. Lett., 1997, 233(1), 25-28.
[] [PMID: 9324231]
Nordborg, C.; Johansson, B.B. Secondary thalamic lesions after ligation of the middle cerebral artery: an ultrastructural study. Acta Neuropathol., 1996, 91(1), 61-66.
[] [PMID: 8773147]
Block, F. Stimulation of N-methyl-D-aspartate receptors in the rat nucleus reticularis thalami suppresses somatosensory evoked potentials. Brain Res., 1994, 636(1), 143-146.
[] [PMID: 7512432]
Ohara, P.T.; Lieberman, A.R. The thalamic reticular nucleus of the adult rat: experimental anatomical studies. J. Neurocytol., 1985, 14(3), 365-411.
[] [PMID: 2413176]
Ni, M.; Lee, A.S. ER chaperones in mammalian development and human diseases. FEBS Lett., 2007, 581(19), 3641-3651.
[] [PMID: 17481612]
Long, F. Building strong bones: molecular regulation of the osteoblast lineage. Nat. Rev. Mol. Cell Biol., 2011, 13(1), 27-38.
[] [PMID: 22189423]
Wang, M.; Wey, S.; Zhang, Y.; Ye, R.; Lee, A.S. Role of the unfolded protein response regulator GRP78/BiP in development, cancer, and neurological disorders. Antioxid. Redox Signal., 2009, 11(9), 2307-2316.
[] [PMID: 19309259]
Lalancette-Hébert, M.; Gowing, G.; Simard, A.; Weng, Y.C.; Kriz, J. Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. J. Neurosci., 2007, 27(10), 2596-2605.
[] [PMID: 17344397]
Szalay, G.; Martinecz, B.; Lénárt, N.; Környei, Z.; Orsolits, B.; Judák, L.; Császár, E.; Fekete, R.; West, B.L.; Katona, G.; Rózsa, B.; Dénes, Á. Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke. Nat. Commun., 2016, 7, 11499.
[] [PMID: 27139776]
Jones, K.A.; Zouikr, I.; Patience, M.; Clarkson, A.N.; Isgaard, J.; Johnson, S.J.; Spratt, N.; Nilsson, M.; Walker, F.R. Chronic stress exacerbates neuronal loss associated with secondary neurodegeneration and suppresses microglial-like cells following focal motor cortex ischemia in the mouse. Brain Behav. Immun., 2015, 48, 57-67.
[] [PMID: 25749481]
Pappata, S.; Levasseur, M.; Gunn, R.N.; Myers, R.; Crouzel, C.; Syrota, A.; Jones, T.; Kreutzberg, G.W.; Banati, R.B. Thalamic microglial activation in ischemic stroke detected in vivo by PET and [11C]PK1195. Neurology, 2000, 55(7), 1052-1054.
[] [PMID: 11061271]
Küry, P.; Schroeter, M.; Jander, S. Transcriptional response to circumscribed cortical brain ischemia: spatiotemporal patterns in ischemic vs. remote non-ischemic cortex. Eur. J. Neurosci., 2004, 19(7), 1708-1720.
[] [PMID: 15078545]
Myers, R.; Manjil, L.G.; Frackowiak, R.S.; Cremer, J.E. [3H]PK 11195 and the localisation of secondary thalamic lesions following focal ischaemia in rat motor cortex. Neurosci. Lett., 1991, 133(1), 20-24.
[] [PMID: 1791992]
Patience, M.J.; Zouikr, I.; Jones, K.; Clarkson, A.N.; Isgaard, J.; Johnson, S.J.; Walker, F.R.; Nilsson, M. Photothrombotic stroke induces persistent ipsilateral and contralateral astrogliosis in key cognitive control nuclei. Neurochem. Res., 2015, 40(2), 362-371.
[] [PMID: 25503479]
Zalewska, K.; Pietrogrande, G.; Ong, L.K.; Abdolhoseini, M.; Kluge, M.; Johnson, S.J.; Walker, F.R.; Nilsson, M. Sustained administration of corticosterone at stress-like levels after stroke suppressed glial reactivity at sites of thalamic secondary neurodegeneration. Brain Behav. Immun., 2018, 69, 210-222.
[] [PMID: 29162554]
Gelosa, P.; Lecca, D.; Fumagalli, M.; Wypych, D.; Pignieri, A.; Cimino, M.; Verderio, C.; Enerbäck, M.; Nikookhesal, E.; Tremoli, E.; Abbracchio, M.P.; Sironi, L. Microglia is a key player in the reduction of stroke damage promoted by the new antithrombotic agent ticagrelor. J. Cereb. Blood Flow Metab., 2014, 34(6), 979-988.
[] [PMID: 24643079]
Ong, L.K.; Zhao, Z.; Kluge, M.; Walker, F.R.; Nilsson, M. Chronic stress exposure following photothrombotic stroke is associated with increased levels of Amyloid beta accumulation and altered oligomerisation at sites of thalamic secondary neurodegeneration in mice. J. Cereb. Blood Flow Metab., 2017, 37(4), 1338-1348.
[] [PMID: 27342322]
Mäkinen, S.; van Groen, T.; Clarke, J.; Thornell, A.; Corbett, D.; Hiltunen, M.; Soininen, H.; Jolkkonen, J. Coaccumulation of calcium and β-amyloid in the thalamus after transient middle cerebral artery occlusion in rats. J. Cereb. Blood Flow Metab., 2008, 28(2), 263-268.
[] [PMID: 17653130]
van Groen, T.; Puurunen, K.; Mäki, H.M.; Sivenius, J.; Jolkkonen, J. Transformation of diffuse β-amyloid precursor protein and β-amyloid deposits to plaques in the thalamus after transient occlusion of the middle cerebral artery in rats. Stroke, 2005, 36(7), 1551-1556.
[] [PMID: 15933257]
Cai, Z.; Hussain, M.D.; Yan, L.J. Microglia, neuroinflammation, and β-amyloid protein in Alzheimer’s disease. Int. J. Neurosci., 2014, 124(5), 307-321.
[] [PMID: 23930978]
Barage, S.H.; Sonawane, K.D. Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer’s disease. Neuropeptides, 2015, 52, 1-18.
[] [PMID: 26149638]
Morris, G.P.; Clark, I.A.; Vissel, B. Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer’s disease. Acta Neuropathol. Commun., 2014, 2, 135-155.
[] [PMID: 25231068]
Zhang, J.; Zhang, Y.; Li, J.; Xing, S.; Li, C.; Li, Y.; Dang, C.; Fan, Y.; Yu, J.; Pei, Z.; Zeng, J. Autophagosomes accumulation is associated with β-amyloid deposits and secondary damage in the thalamus after focal cortical infarction in hypertensive rats. J. Neurochem., 2012, 120(4), 564-573.
[] [PMID: 21950964]
Roberds, S.L.; Anderson, J.; Basi, G.; Bienkowski, M.J.; Branstetter, D.G.; Chen, K.S.; Freedman, S.B.; Frigon, N.L.; Games, D.; Hu, K.; Johnson-Wood, K.; Kappenman, K.E.; Kawabe, T.T.; Kola, I.; Kuehn, R.; Lee, M.; Liu, W.; Motter, R.; Nichols, N.F.; Power, M.; Robertson, D.W.; Schenk, D.; Schoor, M.; Shopp, G.M.; Shuck, M.E.; Sinha, S.; Svensson, K.A.; Tatsuno, G.; Tintrup, H.; Wijsman, J.; Wright, S.; McConlogue, L. BACE knockout mice are healthy despite lacking the primary β-secretase activity in brain: implications for Alzheimer’s disease therapeutics. Hum. Mol. Genet., 2001, 10(12), 1317-1324.
[] [PMID: 11406613]
Vassar, R.; Bennett, B.D.; Babu-Khan, S.; Kahn, S.; Mendiaz, E.A.; Denis, P.; Teplow, D.B.; Ross, S.; Amarante, P.; Loeloff, R.; Luo, Y.; Fisher, S.; Fuller, J.; Edenson, S.; Lile, J.; Jarosinski, M.A.; Biere, A.L.; Curran, E.; Burgess, T.; Louis, J.C.; Collins, F.; Treanor, J.; Rogers, G.; Citron, M. β-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science, 1999, 286(5440), 735-741.
[] [PMID: 10531052]
Pryor, N.E.; Moss, M.A.; Hestekin, C.N. Unraveling the early events of amyloid-β protein (Aβ) aggregation: techniques for the determination of Aβ aggregate size. Int. J. Mol. Sci., 2012, 13(3), 3038-3072.
[] [PMID: 22489141]
Giuffrida, M.L.; Caraci, F.; De Bona, P.; Pappalardo, G.; Nicoletti, F.; Rizzarelli, E.; Copani, A. The monomer state of beta-amyloid: where the Alzheimer’s disease protein meets physiology. Rev. Neurosci., 2010, 21(2), 83-93.
[] [PMID: 20614800]
Lesné, S.; Koh, M.T.; Kotilinek, L.; Kayed, R.; Glabe, C.G.; Yang, A.; Gallagher, M.; Ashe, K.H. A specific amyloid-β protein assembly in the brain impairs memory. Nature, 2006, 440(7082), 352-357.
[] [PMID: 16541076]
Sheikh, S. Safia; Haque, E.; Mir, S.S. Neurodegenerative diseases: multifactorial conformational diseases and their therapeutic interventions. J. Neurodegener. Dis., 2013, 2013563481
[] [PMID: 26316993]
Walsh, D.M.; Klyubin, I.; Fadeeva, J.V.; Cullen, W.K.; Anwyl, R.; Wolfe, M.S.; Rowan, M.J.; Selkoe, D.J. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature, 2002, 416(6880), 535-539.
[] [PMID: 11932745]
Kim, W.S.; Kågedal, K.; Halliday, G.M. Alpha-synuclein biology in Lewy body diseases. Alzheimers Res. Ther., 2014, 6(5), 73-81.
[] [PMID: 25580161]
Takeda, A.; Hasegawa, T.; Matsuzaki-Kobayashi, M.; Sugeno, N.; Kikuchi, A.; Itoyama, Y.; Furukawa, K. Mechanisms of neuronal death in synucleinopathy. J. Biomed. Biotechnol., 2006, 2006(3), 19365.
[PMID: 17047300]
Oueslati, A.; Fournier, M.; Lashuel, H.A. Role of post-translational modifications in modulating the structure, function and toxicity of α-synuclein: implications for Parkinson’s disease pathogenesis and therapies. Prog. Brain Res., 2010, 183, 115-145.
[] [PMID: 20696318]
Zhao, Y.; Chen, F.; Chen, S.; Liu, X.; Cui, M.; Dong, Q. The Parkinson’s disease-associated gene PINK1 protects neurons from ischemic damage by decreasing mitochondrial translocation of the fission promoter Drp1. J. Neurochem., 2013, 127(5), 711-722.
[] [PMID: 23772688]
Schmid, A.W.; Fauvet, B.; Moniatte, M.; Lashuel, H.A. Alpha-synuclein post-translational modifications as potential biomarkers for Parkinson disease and other synucleinopathies. Mol. Cell. Proteomics, 2013, 12(12), 3543-3558.
[] [PMID: 23966418]
Lee, V.M.Y.; Trojanowski, J.Q. Mechanisms of Parkinson’s disease linked to pathological α-synuclein: new targets for drug discovery. Neuron, 2006, 52(1), 33-38.
[] [PMID: 17015225]
Nakka, V.P.; Prakash-Babu, P.; Vemuganti, R. Crosstalk between endoplasmic reticulum stress, oxidative stress, and autophagy: potential therapeutic targets for acute CNS injuries. Mol. Neurobiol., 2016, 53(1), 532-544.
[] [PMID: 25482050]
Dias, V.; Junn, E.; Mouradian, M.M. The role of oxidative stress in Parkinson’s disease. J. Parkinsons Dis., 2013, 3(4), 461-491.
[] [PMID: 24252804]
Kim, T.H.; Vemuganti, R. Effect of sex and age interactions on functional outcome after stroke. CNS Neurosci. Ther., 2015, 21(4), 327-336.
[] [PMID: 25404174]
Strauss, J.H.; Strauss, E.G. The alphaviruses: gene expression, replication, and evolution. Microbiol. Rev., 1994, 58(3), 491-562.
[] [PMID: 7968923]
Glick, D.; Barth, S.; Macleod, K.F.J. Autophagy: cellular and molecular mechanisms. J. Pathol., 2010, 221(1), 3-12.
[] [PMID: 20225336]
Yang, Z.; Klionsky, D.J. An overview of the molecular mechanism of autophagy.Autophagy in infect and immunity; Levine, B.; Yoshimori, T; Deretic, V., Ed.; Springer: Berlin-Heidelberg, Germany, 2009, pp. 1-32.
Uchiyama, Y.; Koike, M.; Shibata, M. Autophagic neuron death in neonatal brain ischemia/hypoxia. Autophagy, 2008, 4(4), 404-408.
[] [PMID: 18212531]
Rami, A.; Langhagen, A.; Steiger, S. Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death. Neurobiol. Dis., 2008, 29(1), 132-141.
[] [PMID: 17936001]
Laussmann, M.A.; Passante, E.; Hellwig, C.T.; Tomiczek, B.; Flanagan, L.; Prehn, J.H.; Huber, H.J.; Rehm, M. Proteasome inhibition can impair caspase-8 activation upon submaximal stimulation of apoptotic tumor necrosis factor-related apoptosis inducing ligand (TRAIL) signaling. J. Biol. Chem., 2012, 287(18), 14402-14411.
[] [PMID: 22408249]
Zeng, X.; Overmeyer, J.H.; Maltese, W.A. Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking. J. Cell Sci., 2006, 119(Pt 2), 259-270.
[] [PMID: 16390869]
Xing, S.; Zhang, Y.; Li, J.; Zhang, J.; Li, Y.; Dang, C.; Li, C.; Fan, Y.; Yu, J.; Pei, Z.; Zeng, J. Beclin 1 knockdown inhibits autophagic activation and prevents the secondary neurodegenerative damage in the ipsilateral thalamus following focal cerebral infarction. Autophagy, 2012, 8(1), 63-76.
[] [PMID: 22108007]
Jones, K.A.; Maltby, S.; Plank, M.W.; Kluge, M.; Nilsson, M.; Foster, P.S.; Walker, F.R. Peripheral immune cells infiltrate into sites of secondary neurodegeneration after ischemic stroke. Brain Behav. Immun., 2018, 67, 299-307.
[] [PMID: 28911981]
Yang, Z.; Yu, A.; Liu, Y.; Shen, H.; Lin, C.; Lin, L.; Wang, S.; Yuan, B. Regulatory T cells inhibit microglia activation and protect against inflammatory injury in intracerebral hemorrhage. Int. Immunopharmacol., 2014, 22(2), 522-525.
[] [PMID: 25000335]
Morrison, H.W.; Filosa, J.A. A quantitative spatiotemporal analysis of microglia morphology during ischemic stroke and reperfusion. J. Neuroinflammation, 2013, 10, 4.
[] [PMID: 23311642]
Sasaki, A. Microglia and brain macrophages: An update. Neuropathology, 2017, 37(5), 452-464.
[] [PMID: 27859676]
Boche, D.; Perry, V.H.; Nicoll, J.A. Review: activation patterns of microglia and their identification in the human brain. Neuropathol. Appl. Neurobiol., 2013, 39(1), 3-18.
[] [PMID: 23252647]
Graham, N.S.; Sharp, D.J. Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia. J. Neurol. Neurosurg. Psychiatry, 2019, 90(11), 1221-1233.
[] [PMID: 31542723]
Cruz-Haces, M.; Tang, J.; Acosta, G.; Fernandez, J.; Shi, R. Pathological correlations between traumatic brain injury and chronic neurodegenerative diseases. Transl. Neurodegener., 2017, 6, 20-29.
[] [PMID: 28702179]
Goldman, S.M.; Tanner, C.M.; Oakes, D.; Bhudhikanok, G.S.; Gupta, A.; Langston, J.W. Head injury and Parkinson’s disease risk in twins. Ann. Neurol., 2006, 60(1), 65-72.
[] [PMID: 16718702]
Hicks, R.R.; Smith, D.H.; Lowenstein, D.H.; Saint Marie, R.; McIntosh, T.K. Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus. J. Neurotrauma, 1993, 10(4), 405-414.
[] [PMID: 8145264]
Šimić, G.; Lucassen, P.J.; Krsnik, Z.; Krušlin, B.; Kostović, I.; Winblad, B.; Bogdanovi, nNOS expression in reactive astrocytes correlates with increased cell death related DNA damage in the hippocampus and entorhinal cortex in Alzheimer’s disease. Exp. Neurol., 2000, 165(1), 12-26.
[] [PMID: 10964481]
Wilde, E.A.; Bigler, E.D.; Hunter, J.V.; Fearing, M.A.; Scheibel, R.S.; Newsome, M.R.; Johnson, J.L.; Bachevalier, J.; Li, X.; Levin, H.S. Hippocampus, amygdala, and basal ganglia morphometrics in children after moderate-to-severe traumatic brain injury. Dev. Med. Child Neurol., 2007, 49(4), 294-299.
[] [PMID: 17376141]
Carlsson, M.; Carlsson, A. Interactions between glutamatergic and monoaminergic systems within the basal ganglia--implications for schizophrenia and Parkinson’s disease. Trends Neurosci., 1990, 13(7), 272-276.
[] [PMID: 1695402]
Huang, C.H.; Lin, C.W.; Lee, Y.C.; Huang, C.Y.; Huang, R.Y.; Tai, Y.C.; Wang, K.W.; Yang, S.N.; Sun, Y.T.; Wang, H.K. Is traumatic brain injury a risk factor for neurodegeneration? A meta-analysis of population-based studies. BMC Neurol., 2018, 18(1), 184-191.
[] [PMID: 30396335]
Wang, H.K.; Lee, Y.C.; Huang, C.Y.; Liliang, P.C.; Lu, K.; Chen, H.J.; Li, Y.C.; Tsai, K.J. Traumatic brain injury causes frontotemporal dementia and TDP-43 proteolysis. Neuroscience, 2015, 300, 94-103.
[] [PMID: 25982564]
Chen, H.; Richard, M.; Sandler, D.P.; Umbach, D.M.; Kamel, F. Head injury and amyotrophic lateral sclerosis. Am. J. Epidemiol., 2007, 166(7), 810-816.
[] [PMID: 17641152]
Schaffert, J.; LoBue, C.; White, C.L.; Chiang, H.S.; Didehbani, N.; Lacritz, L.; Rossetti, H.; Dieppa, M.; Hart, J.; Cullum, C.M. Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer’s disease. Neuropsychology, 2018, 32(4), 410-416.
[] [PMID: 29389151]
Tagge, C.A.; Fisher, A.M.; Minaeva, O.V.; Gaudreau-Balderrama, A.; Moncaster, J.A.; Zhang, X.L.; Wojnarowicz, M.W.; Casey, N.; Lu, H.; Kokiko-Cochran, O.N.; Saman, S.; Ericsson, M.; Onos, K.D.; Veksler, R.; Senatorov, V.V., Jr; Kondo, A.; Zhou, X.Z.; Miry, O.; Vose, L.R.; Gopaul, K.R.; Upreti, C.; Nowinski, C.J.; Cantu, R.C.; Alvarez, V.E.; Hildebrandt, A.M.; Franz, E.S.; Konrad, J.; Hamilton, J.A.; Hua, N.; Tripodis, Y.; Anderson, A.T.; Howell, G.R.; Kaufer, D.; Hall, G.F.; Lu, K.P.; Ransohoff, R.M.; Cleveland, R.O.; Kowall, N.W.; Stein, T.D.; Lamb, B.T.; Huber, B.R.; Moss, W.C.; Friedman, A.; Stanton, P.K.; McKee, A.C.; Goldstein, L.E. Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model. Brain, 2018, 141(2), 422-458.
[] [PMID: 29360998]
Johnson, V.E.; Stewart, J.E.; Begbie, F.D.; Trojanowski, J.Q.; Smith, D.H.; Stewart, W. Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain, 2013, 136(Pt 1), 28-42.
[] [PMID: 23365092]
Ly, J.V.; Rowe, C.C.; Villemagne, V.L.; Zavala, J.A.; Ma, H.; Sahathevan, R.; O’Keefe, G.; Gong, S.J.; Gunawan, R.; Churilov, L.; Saunder, T.; Ackerman, U.; Tochon-Danguy, H.; Donnan, G.A. Subacute ischemic stroke is associated with focal 11C PiB positron emission tomography retention but not with global neocortical Aβ deposition. Stroke, 2012, 43(5), 1341-1346.
[] [PMID: 22492514]
Liu, W.; Wong, A.; Au, L.; Yang, J.; Wang, Z.; Leung, E.Y.; Chen, S.; Ho, C.L.; Mok, V.C. Influence of amyloid-β on cognitive decline after stroke/transient ischemic attack: three-year longitudinal study. Stroke, 2015, 46(11), 3074-3080.
[] [PMID: 26382174]
Sahathevan, R.; Linden, T.; Villemagne, V.L.; Churilov, L.; Ly, J.V.; Rowe, C.; Donnan, G.; Brodtmann, A. Positron emission tomographic imaging in stroke: cross-sectional and follow-up assessment of amyloid in ischemic stroke. Stroke, 2016, 47(1), 113-119.
[] [PMID: 26578658]
Tamura, A.; Tahira, Y.; Nagashima, H.; Kirino, T.; Gotoh, O.; Hojo, S.; Sano, K. Thalamic atrophy following cerebral infarction in the territory of the middle cerebral artery. Stroke, 1991, 22(5), 615-618.
[] [PMID: 2028491]
Ogawa, T.; Yoshida, Y.; Okudera, T.; Noguchi, K.; Kado, H.; Uemura, K. Secondary thalamic degeneration after cerebral infarction in the middle cerebral artery distribution: evaluation with MR imaging. Radiology, 1997, 204(1), 255-262.
[] [PMID: 9205256]
Nakane, M.; Tamura, A.; Sasaki, Y.; Teraoka, A. MRI of secondary changes in the thalamus following a cerebral infarct. Neuroradiology, 2002, 44(11), 915-920.
[] [PMID: 12428126]
Buffon, F.; Molko, N.; Hervé, D.; Porcher, R.; Denghien, I.; Pappata, S.; Le Bihan, D.; Bousser, M.G.; Chabriat, H. Longitudinal diffusion changes in cerebral hemispheres after MCA infarcts. J. Cereb. Blood Flow Metab., 2005, 25(5), 641-650.
[] [PMID: 15689956]
Stocchetti, N.; Protti, A.; Lattuada, M.; Magnoni, S.; Longhi, L.; Ghisoni, L.; Egidi, M.; Zanier, E.R. Impact of pyrexia on neurochemistry and cerebral oxygenation after acute brain injury. J. Neurol. Neurosurg. Psychiatry, 2005, 76(8), 1135-1139.
[] [PMID: 16024893]
Li, C.; Ling, X.; Liu, S.; Xu, A.; Zhang, Y.; Xing, S.; Pei, Z.; Zeng, J. Early detection of secondary damage in ipsilateral thalamus after acute infarction at unilateral corona radiata by diffusion tensor imaging and magnetic resonance spectroscopy. BMC Neurol., 2011, 11, 49-56.
[] [PMID: 21542942]
Gerhard, A.; Schwarz, J.; Myers, R.; Wise, R.; Banati, R.B. Evolution of microglial activation in patients after ischemic stroke: a [11C](R)-PK11195 PET study. Neuroimage, 2005, 24(2), 591-595.
[] [PMID: 15627603]
Fujie, W.; Kirino, T.; Tomukai, N.; Iwasawa, T.; Tamura, A. Progressive shrinkage of the thalamus following middle cerebral artery occlusion in rats. Stroke, 1990, 21(10), 1485-1488.
[] [PMID: 2219214]
Dihné, M.; Grommes, C.; Lutzenburg, M.; Witte, O.W.; Block, F. Different mechanisms of secondary neuronal damage in thalamic nuclei after focal cerebral ischemia in rats. Stroke, 2002, 33(12), 3006-3011.
[] [PMID: 12468804]
Justicia, C.; Ramos-Cabrer, P.; Hoehn, M. MRI detection of secondary damage after stroke: chronic iron accumulation in the thalamus of the rat brain. Stroke, 2008, 39(5), 1541-1547.
[] [PMID: 18323485]
Bihel, E.; Pro-Sistiaga, P.; Letourneur, A.; Toutain, J.; Saulnier, R.; Insausti, R.; Bernaudin, M.; Roussel, S.; Touzani, O. Permanent or transient chronic ischemic stroke in the non-human primate: behavioral, neuroimaging, histological, and immunohistochemical investigations. J. Cereb. Blood Flow Metab., 2010, 30(2), 273-285.
[] [PMID: 19794396]
Lipsanen, A.; Kalesnykas, G.; Pro-Sistiaga, P.; Hiltunen, M.; Vanninen, R.; Bernaudin, M.; Touzani, O.; Jolkkonen, J. Lack of secondary pathology in the thalamus after focal cerebral ischemia in nonhuman primates. Exp. Neurol., 2013, 248, 224-227.
[] [PMID: 23810737]
Bulte, J.W.M.; Modo, M.M.J. Introduction: The emergence of nanoparticles as imaging platform n biomedicine. In: Nanoparticles Biomedical imaging: emerging technologies and applications; Bulte, J.W.M.; Modo, M.M.J., Eds.; Springer-Verlag: New York, 2007; pp. 1-5.
Wickline, S.A.; Lanza, G.M.J. Molecular imaging, targeted therapeutics, and nanoscience. J. Cell. Biochem. Suppl., 2002, 39, 90-97.
[] [PMID: 12552608]
Markus, R.; Donnan, G.; Kazui, S.; Read, S.; Reutens, D. Penumbral topography in human stroke: methodology and validation of the ‘Penumbragram’. Neuroimage, 2004, 21(4), 1252-1259.
[] [PMID: 15050553]
Kolla, N.J.; Houle, S. Single-photon emission computed tomography and positron emission tomography studies of antisocial personality disorder and aggression: a targeted review. Curr. Psychiatry Rep., 2019, 21(4), 24-34.
[] [PMID: 30852703]
Zhang, Y.; Xing, S.; Zhang, J.; Li, J.; Li, C.; Pei, Z.; Zeng, J. Reduction of β-amyloid deposits by γ-secretase inhibitor is associated with the attenuation of secondary damage in the ipsilateral thalamus and sensory functional improvement after focal cortical infarction in hypertensive rats. J. Cereb. Blood Flow Metab., 2011, 31(2), 572-579.
[] [PMID: 20683452]
Sarajärvi, T.; Lipsanen, A.; Mäkinen, P.; Peräniemi, S.; Soininen, H.; Haapasalo, A.; Jolkkonen, J.; Hiltunen, M. Bepridil decreases Aβ and calcium levels in the thalamus after middle cerebral artery occlusion in rats. J. Cell. Mol. Med., 2012, 16(11), 2754-2767.
[] [PMID: 22805236]
Mitkari, B.; Kerkelä, E.; Nystedt, J.; Korhonen, M.; Jolkkonen, J. Unexpected complication in a rat stroke model: exacerbation of secondary pathology in the thalamus by subacute intraarterial administration of human bone marrow-derived mesenchymal stem cells. J. Cereb. Blood Flow Metab., 2015, 35(3), 363-366.
[] [PMID: 25564231]
Kronenberg, G.; Balkaya, M.; Prinz, V.; Gertz, K.; Ji, S.; Kirste, I.; Heuser, I.; Kampmann, B.; Hellmann-Regen, J.; Gass, P.; Sohr, R.; Hellweg, R.; Waeber, C.; Juckel, G.; Hörtnagl, H.; Stumm, R.; Endres, M. Exofocal dopaminergic degeneration as antidepressant target in mouse model of poststroke depression. Biol. Psychiatry, 2012, 72(4), 273-281.
[] [PMID: 22464799]
Ni, J.W.; Takahashi, M.; Yatsugi, S.; Shimizu-Sasamata, M.; Yamaguchi, T. Effects of YM872 on atrophy of substantia nigra reticulata after focal ischemia in rats. Neuroreport, 1998, 9(16), 3719-3724.
[] [PMID: 9858385]
Tennant, K.A.; Taylor, S.L.; White, E.R.; Brown, C.E. Optogenetic rewiring of thalamocortical circuits to restore function in the stroke injured brain. Nat. Commun., 2017, 8, 15879.
[] [PMID: 28643802]
Cheng, M.Y.; Wang, E.H.; Woodson, W.J.; Wang, S.; Sun, G.; Lee, A.G.; Arac, A.; Fenno, L.E.; Deisseroth, K.; Steinberg, G.K. Optogenetic neuronal stimulation promotes functional recovery after stroke. Proc. Natl. Acad. Sci. USA, 2014, 111(35), 12913-12918.
[] [PMID: 25136109]
He, X.; Lu, Y.; Lin, X.; Jiang, L.; Tang, Y.; Tang, G.; Chen, X.; Zhang, Z.; Wang, Y.; Yang, G.Y. Optical inhibition of striatal neurons promotes focal neurogenesis and neurobehavioral recovery in mice after middle cerebral artery occlusion. J. Cereb. Blood Flow Metab., 2017, 37(3), 837-847.
[] [PMID: 27055780]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 15 April, 2020
Page: [1154 - 1168]
Pages: 15
DOI: 10.2174/1568026620666200416090820
Price: $65

Article Metrics

PDF: 29
PRC: 1