Acute histopathological responses and long-term behavioral outcomes in mice with graded controlled cortical impact injury
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摘要
While animal models of controlled cortical impact often display short-term motor dysfunction after injury, histological examinations do not show severe cortical damage. Thus, this model requires further improvement. Mice were subjected to injury at three severities using a Pin-Point~(TM)-controlled cortical impact device to establish secondary brain injury mouse models. Twenty-four hours after injury, hematoxylin-eosin staining, Fluoro-Jade B histofluorescence, and immunohistochemistry were performed for brain slices. Compared to the uninjured side, we observed differences of histopathological findings, neuronal degeneration, and glial cell number in the CA2 and CA3 regions of the hippocampus on the injured side. The Morris water maze task and beam-walking test verified long-term(14–28 days) spatial learning/memory and motor balance. To conclude, the histopathological responses were positively correlated with the degree of damage,as were the long-term behavioral manifestations after controlled cortical impact. All animal procedures were approved by the Institutional Animal Care and Use Committee at Shanghai Jiao Tong University School of Medicine.
While animal models of controlled cortical impact often display short-term motor dysfunction after injury, histological examinations do not show severe cortical damage. Thus, this model requires further improvement. Mice were subjected to injury at three severities using a Pin-Point~(TM)-controlled cortical impact device to establish secondary brain injury mouse models. Twenty-four hours after injury, hematoxylin-eosin staining, Fluoro-Jade B histofluorescence, and immunohistochemistry were performed for brain slices. Compared to the uninjured side, we observed differences of histopathological findings, neuronal degeneration, and glial cell number in the CA2 and CA3 regions of the hippocampus on the injured side. The Morris water maze task and beam-walking test verified long-term(14–28 days) spatial learning/memory and motor balance. To conclude, the histopathological responses were positively correlated with the degree of damage,as were the long-term behavioral manifestations after controlled cortical impact. All animal procedures were approved by the Institutional Animal Care and Use Committee at Shanghai Jiao Tong University School of Medicine.
While animal models of controlled cortical impact often display short-term motor dysfunction after injury, histological examinations do not show severe cortical damage. Thus, this model requires further improvement. Mice were subjected to injury at three severities using a Pin-Point~(TM)-controlled cortical impact device to establish secondary brain injury mouse models. Twenty-four hours after injury, hematoxylin-eosin staining, Fluoro-Jade B histofluorescence, and immunohistochemistry were performed for brain slices. Compared to the uninjured side, we observed differences of histopathological findings, neuronal degeneration, and glial cell number in the CA2 and CA3 regions of the hippocampus on the injured side. The Morris water maze task and beam-walking test verified long-term(14–28 days) spatial learning/memory and motor balance. To conclude, the histopathological responses were positively correlated with the degree of damage,as were the long-term behavioral manifestations after controlled cortical impact. All animal procedures were approved by the Institutional Animal Care and Use Committee at Shanghai Jiao Tong University School of Medicine.
引文
Albert-Weissenberger C,Sirén AL(2010)Experimental traumatic brain injury.Exp Transl Stroke Med 2:16.
Bilgen M(2005)A new device for experimental modeling of central nervous system injuries.Neurorehabil Neural Repair 19:219-226.
Cao Y,Gao Y,Xu S,Bao J,Lin Y,Luo X,Wang Y,Luo Q,Jiang J,Neale JH,Zhong C(2016)Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.BMC Neurosci 17:15.
Chen S,Pickard JD,Harris NG(2003)Time course of cellular pathology after controlled cortical impact injury.Exp Neurol182:87-102.
Chen T,Yu Y,Tang LJ,Kong L,Zhang CH,Chu HY,Yin LW,Ma HY(2017)Neural stem cells over-expressing brain-derived neurotrophic factor promote neuronal survival and cytoskeletal protein expression in traumatic brain injury sites.Neural Regen Res12:433-439.
Dixon CE,Clifton GL,Lighthall JW,Yaghmai AA,Hayes RL(1991)A controlled cortical impact model of traumatic brain injury in the rat.J Neurosci Methods 39:253-262.
Dunn-Meynell AA,Levin BE(1997)Histological markers of neuronal,axonal and astrocytic changes after lateral rigid impact traumatic brain injury.Brain Res 761:25-41.
Dvela-Levitt M,Ami HC-B,Rosen H,Shohami E,Lichtstein D(2014)Ouabain improves functional recovery following traumatic brain injury.J Neurotrauma 31:1942-1947.
Ekmark-Lewén S,Lewén A,Israelsson C,Li GL,Farooque M,Olsson Y,Ebendal T,Hillered L(2010)Vimentin and GFAP responses in astrocytes after contusion trauma to the murine brain.Restor Neurol Neurosci 28:311-321.
Fox GB,Fan L,Levasseur RA,Faden AI(1998)Sustained sensory/motor and cognitive deficits with neuronal apoptosis following controlled cortical impact brain injury in the mouse.J Neurotrauma 15:599-614.
Freyaldenhoven TE,Ali SF,Schmued LC(1997)Systemic administration of MPTP induces thalamic neuronal degeneration in mice.Brain Res 759:9-17.
Gao Y,Xu S,Cui Z,Zhang M,Lin Y,Cai L,Wang Z,Luo X,Zheng Y,Wang Y,Luo Q,Jiang J,Neale JH,Zhong C(2015)Mice lacking glutamate carboxypeptidase II develop normally,but are less susceptible to traumatic brain injury.J Neurochem 134:340-353.
Guerriero RM,Giza CC,Rotenberg A(2015)Glutamate and GABA imbalance following traumatic brain injury.Curr Neurol Neurosci Rep 15:27.
Hellewell SC,Yan EB,Agyapomaa DA,Bye N,Morganti-Kossmann MC(2010)Post-traumatic hypoxia exacerbates brain tissue damage:analysis of axonal injury and glial responses.JNeurotrauma 27:1997-2010.
Huang XJ,Glushakova O,Mondello S,Van K,Hayes RL,Lyeth BG(2015)Acute temporal profiles of serum levels of UCH-L1 and GFAP and relationships to neuronal and astroglial pathology following traumatic brain injury in rats.J Neurotrauma 32:1179-1189.
Hunt RF,Scheff SW,Smith BN(2009)Posttraumatic epilepsy after controlled cortical impact injury in mice.Exp Neurol 215:243-252.
Isoniemi H,Kurki T,Tenovuo O,Kairisto V,Portin R(2006)Hippocampal volume,brain atrophy,and APOE genotype after traumatic brain injury.Neurology 67:756-760.
Jiang L,Hu Y,He X,Lv Q,Wang TH,Xia QJ(2017)Breviscapine reduces neuronal injury caused by traumatic brain injury insult:partly associated with suppression of interleukin-6 expression.Neural Regen Res 12:90-95.
Kunkler PE,Kraig RP(1997)Reactive astrocytosis from excitotoxic injury in hippocampal organ culture parallels that seen in vivo.JCereb Blood Flow Metab 17:26-43.
Liu D,Smith CL,Barone FC,Ellison JA,Lysko PG,Li K,Simpson IA(1999)Astrocytic demise precedes delayed neuronal death in focal ischemic rat brain.Brain Res Mol Brain Res 68:29-41.
Loane DJ,Faden AI(2010)Neuroprotection for traumatic brain injury:translational challenges and emerging therapeutic strategies.Trends Pharmacol Sci 31:596-604.
Marklund N,Hillered L(2011)Animal modelling of traumatic brain injury in preclinical drug development:where do we go from here?Br J Pharmacol 164:1207-1229.
McCarthy MM(2003)Stretching the truth:Why hippocampal neurons are so vulnerable following traumatic brain injury.Exp Neurol 184:40-43.
Morales DM,Marklund N,Lebold D,Thompson HJ,Pitkanen A,Maxwell WL,Longhi L,Laurer H,Maegele M,Neugebauer E,Graham DI,Stocchetti N,McIntosh TK(2005)Experimental models of traumatic brain injury:Do we really need to build a better mousetrap?Neuroscience 136:971-989.
Morris RG,G0arrud P,Rawlins JN,O’Keefe J(1982)Place navigation impaired in rats with hippocampal lesions.Nature 297:681-683.
Rola R,Mizumatsu S,Otsuka S,Morhardt DR,Noble-Haeusslein LJ,Fishman K,Potts MB,Fike JR(2006)Alterations in hippocampal neurogenesis following traumatic brain injury in mice.Exp Neurol 202:189-199.
Saatman KE,Feeko KJ,Pape RL,Raghupathi R(2006)Differential behavioral and histopathological responses to graded cortical impact injury in mice.J Neurotrauma 23:1241-1253.
Scheff SW,Rabchevsky AG,Fugaccia I,Main JA,Lumpp JE(2003)Experimental modeling of spinal cord injury:characterization of a force-defined injury device.J Neurotrauma 20:179-193.
Schmued LC,Albertson C,Slikker W Jr(1997)Fluoro-Jade:a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration.Brain Res 751:37-46.
Shear DA,Tate MC,Archer DR,Hoffman SW,Hulce VD,LaPlaca MC,Stein DG(2004)Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury.Brain Res 1026:11-22.
Smith DH,Soares HD,Pierce JS,Perlman KG,Saatman KE,Meaney DF,Dixon CE,McIntosh TK(1995)A model of parasagittal controlled cortical impact in the mouse:cognitive and histopathologic effects.J Neurotrauma 12:169-178.
Thompson HJ,Lifshitz J,Marklund N,Grady MS,Graham DI,Hovda DA,McIntosh TK(2005)Lateral fluid percussion brain injury:a 15-year review and evaluation.J Neurotrauma 22:42-75.
von Baumgarten L,Trabold R,Thal S,Back T,Plesnila N(2008)Role of cortical spreading depressions for secondary brain damage after traumatic brain injury in mice.J Cereb Blood Flow Metab 28:1353-1360.
Wang D,Xu X,Wu YG,Lyu L,Zhou ZW,Zhang JN(2018)Dexmedetomidine attenuates traumatic brain injury:action pathway and mechanisms.Neural Regen Res 13:819-826.
Xu HH,Dong HJ,Shang CZ,Zhao ML(2017)Umbilical cord mesenchymal stem cell transplantation increases microvessel density in surrounding areas of acute traumatic brain injury in rats.Zhongguo Zuzhi Gongcheng Yanjiu 21:5320-5324.
Zhao X,Ahram A,Berman RF,Muizelaar JP,Lyeth BG(2003)Early loss of astrocytes after experimental traumatic brain injury.Glia 44:140-152.
Zhong C,Zhao X,Sarva J,Kozikowski A,Neale JH,Lyeth BG(2005)NAAG peptidase inhibitor reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion TBI in rats.J Neurotrauma 22:266-276.
Bilgen M(2005)A new device for experimental modeling of central nervous system injuries.Neurorehabil Neural Repair 19:219-226.
Cao Y,Gao Y,Xu S,Bao J,Lin Y,Luo X,Wang Y,Luo Q,Jiang J,Neale JH,Zhong C(2016)Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.BMC Neurosci 17:15.
Chen S,Pickard JD,Harris NG(2003)Time course of cellular pathology after controlled cortical impact injury.Exp Neurol182:87-102.
Chen T,Yu Y,Tang LJ,Kong L,Zhang CH,Chu HY,Yin LW,Ma HY(2017)Neural stem cells over-expressing brain-derived neurotrophic factor promote neuronal survival and cytoskeletal protein expression in traumatic brain injury sites.Neural Regen Res12:433-439.
Dixon CE,Clifton GL,Lighthall JW,Yaghmai AA,Hayes RL(1991)A controlled cortical impact model of traumatic brain injury in the rat.J Neurosci Methods 39:253-262.
Dunn-Meynell AA,Levin BE(1997)Histological markers of neuronal,axonal and astrocytic changes after lateral rigid impact traumatic brain injury.Brain Res 761:25-41.
Dvela-Levitt M,Ami HC-B,Rosen H,Shohami E,Lichtstein D(2014)Ouabain improves functional recovery following traumatic brain injury.J Neurotrauma 31:1942-1947.
Ekmark-Lewén S,Lewén A,Israelsson C,Li GL,Farooque M,Olsson Y,Ebendal T,Hillered L(2010)Vimentin and GFAP responses in astrocytes after contusion trauma to the murine brain.Restor Neurol Neurosci 28:311-321.
Fox GB,Fan L,Levasseur RA,Faden AI(1998)Sustained sensory/motor and cognitive deficits with neuronal apoptosis following controlled cortical impact brain injury in the mouse.J Neurotrauma 15:599-614.
Freyaldenhoven TE,Ali SF,Schmued LC(1997)Systemic administration of MPTP induces thalamic neuronal degeneration in mice.Brain Res 759:9-17.
Gao Y,Xu S,Cui Z,Zhang M,Lin Y,Cai L,Wang Z,Luo X,Zheng Y,Wang Y,Luo Q,Jiang J,Neale JH,Zhong C(2015)Mice lacking glutamate carboxypeptidase II develop normally,but are less susceptible to traumatic brain injury.J Neurochem 134:340-353.
Guerriero RM,Giza CC,Rotenberg A(2015)Glutamate and GABA imbalance following traumatic brain injury.Curr Neurol Neurosci Rep 15:27.
Hellewell SC,Yan EB,Agyapomaa DA,Bye N,Morganti-Kossmann MC(2010)Post-traumatic hypoxia exacerbates brain tissue damage:analysis of axonal injury and glial responses.JNeurotrauma 27:1997-2010.
Huang XJ,Glushakova O,Mondello S,Van K,Hayes RL,Lyeth BG(2015)Acute temporal profiles of serum levels of UCH-L1 and GFAP and relationships to neuronal and astroglial pathology following traumatic brain injury in rats.J Neurotrauma 32:1179-1189.
Hunt RF,Scheff SW,Smith BN(2009)Posttraumatic epilepsy after controlled cortical impact injury in mice.Exp Neurol 215:243-252.
Isoniemi H,Kurki T,Tenovuo O,Kairisto V,Portin R(2006)Hippocampal volume,brain atrophy,and APOE genotype after traumatic brain injury.Neurology 67:756-760.
Jiang L,Hu Y,He X,Lv Q,Wang TH,Xia QJ(2017)Breviscapine reduces neuronal injury caused by traumatic brain injury insult:partly associated with suppression of interleukin-6 expression.Neural Regen Res 12:90-95.
Kunkler PE,Kraig RP(1997)Reactive astrocytosis from excitotoxic injury in hippocampal organ culture parallels that seen in vivo.JCereb Blood Flow Metab 17:26-43.
Liu D,Smith CL,Barone FC,Ellison JA,Lysko PG,Li K,Simpson IA(1999)Astrocytic demise precedes delayed neuronal death in focal ischemic rat brain.Brain Res Mol Brain Res 68:29-41.
Loane DJ,Faden AI(2010)Neuroprotection for traumatic brain injury:translational challenges and emerging therapeutic strategies.Trends Pharmacol Sci 31:596-604.
Marklund N,Hillered L(2011)Animal modelling of traumatic brain injury in preclinical drug development:where do we go from here?Br J Pharmacol 164:1207-1229.
McCarthy MM(2003)Stretching the truth:Why hippocampal neurons are so vulnerable following traumatic brain injury.Exp Neurol 184:40-43.
Morales DM,Marklund N,Lebold D,Thompson HJ,Pitkanen A,Maxwell WL,Longhi L,Laurer H,Maegele M,Neugebauer E,Graham DI,Stocchetti N,McIntosh TK(2005)Experimental models of traumatic brain injury:Do we really need to build a better mousetrap?Neuroscience 136:971-989.
Morris RG,G0arrud P,Rawlins JN,O’Keefe J(1982)Place navigation impaired in rats with hippocampal lesions.Nature 297:681-683.
Rola R,Mizumatsu S,Otsuka S,Morhardt DR,Noble-Haeusslein LJ,Fishman K,Potts MB,Fike JR(2006)Alterations in hippocampal neurogenesis following traumatic brain injury in mice.Exp Neurol 202:189-199.
Saatman KE,Feeko KJ,Pape RL,Raghupathi R(2006)Differential behavioral and histopathological responses to graded cortical impact injury in mice.J Neurotrauma 23:1241-1253.
Scheff SW,Rabchevsky AG,Fugaccia I,Main JA,Lumpp JE(2003)Experimental modeling of spinal cord injury:characterization of a force-defined injury device.J Neurotrauma 20:179-193.
Schmued LC,Albertson C,Slikker W Jr(1997)Fluoro-Jade:a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration.Brain Res 751:37-46.
Shear DA,Tate MC,Archer DR,Hoffman SW,Hulce VD,LaPlaca MC,Stein DG(2004)Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury.Brain Res 1026:11-22.
Smith DH,Soares HD,Pierce JS,Perlman KG,Saatman KE,Meaney DF,Dixon CE,McIntosh TK(1995)A model of parasagittal controlled cortical impact in the mouse:cognitive and histopathologic effects.J Neurotrauma 12:169-178.
Thompson HJ,Lifshitz J,Marklund N,Grady MS,Graham DI,Hovda DA,McIntosh TK(2005)Lateral fluid percussion brain injury:a 15-year review and evaluation.J Neurotrauma 22:42-75.
von Baumgarten L,Trabold R,Thal S,Back T,Plesnila N(2008)Role of cortical spreading depressions for secondary brain damage after traumatic brain injury in mice.J Cereb Blood Flow Metab 28:1353-1360.
Wang D,Xu X,Wu YG,Lyu L,Zhou ZW,Zhang JN(2018)Dexmedetomidine attenuates traumatic brain injury:action pathway and mechanisms.Neural Regen Res 13:819-826.
Xu HH,Dong HJ,Shang CZ,Zhao ML(2017)Umbilical cord mesenchymal stem cell transplantation increases microvessel density in surrounding areas of acute traumatic brain injury in rats.Zhongguo Zuzhi Gongcheng Yanjiu 21:5320-5324.
Zhao X,Ahram A,Berman RF,Muizelaar JP,Lyeth BG(2003)Early loss of astrocytes after experimental traumatic brain injury.Glia 44:140-152.
Zhong C,Zhao X,Sarva J,Kozikowski A,Neale JH,Lyeth BG(2005)NAAG peptidase inhibitor reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion TBI in rats.J Neurotrauma 22:266-276.