Cerebellum was shown to be vulnerable to traumatic brain injury (TBI) in experimental animals. However, the detailed pathological and functional changes within the cerebellum following TBI are not known. Using our established cerebellum fluid percussion injury (FPI) model, we characterized the temporal pattern and the nature of structural damage following FPI, as well as the functional changes of Purkinje cells in response to climbing fiber activation. Our results showed that 60% of Purkinje cells died within the first 24 h following moderate FPI. In contrast, clusters of densely stained shrunken granule cells were stained positive for terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) in 1, 3 or 7 days following FPI animals. We also observed an accompanying structural damage to the cerebellar white matter tract. Disconnected axonal fibers appeared 1 day post-FPI, and loss of white matter fibers were visible 3 and 7 days post-FPI. Massive accumulation of β-amyloid precursor protein (βAPP) was found in the white matter tracts and molecular layer in the cerebellum of 1, 3 or 7 days FPI animals. Our functional study showed that the majority of Purkinje cells from 1 day and all cells from 3 to 7 days post-FPI had distorted membrane potential and synaptic responses to climbing fiber activation. These results suggested that there is a co-related structural and functional deterioration with a specific temporal pattern in the cerebellum following FPI. These observations provide a basis for future mechanistic investigations aiming to realize neuroprotection from cerebellar neuronal death and loss of cerebellar functionality.
机构:
Univ Calif Los Angeles, Neurosurg, Los Angeles, CA USA
Univ Calif Los Angeles, Psychol, Los Angeles, CA USA
Univ Calif Los Angeles, Staglin Ctr Brain & Behav Hlth, Los Angeles, CA USAUniv Calif Los Angeles, Neurosurg, Los Angeles, CA USA
Hoffman, Ann
Watson, Sonya
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Univ Calif Los Angeles, Neurosurg, Los Angeles, CA USA
Univ Calif Los Angeles, Psychol, Los Angeles, CA USAUniv Calif Los Angeles, Neurosurg, Los Angeles, CA USA
Watson, Sonya
Makridis, Anna
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Univ Calif Los Angeles, Psychol, Los Angeles, CA USAUniv Calif Los Angeles, Neurosurg, Los Angeles, CA USA
Makridis, Anna
Patel, Anisha
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Univ Calif Los Angeles, Psychol, Los Angeles, CA USAUniv Calif Los Angeles, Neurosurg, Los Angeles, CA USA
Patel, Anisha
Giza, Christopher
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Univ Calif Los Angeles, Neurosurg, Los Angeles, CA USAUniv Calif Los Angeles, Neurosurg, Los Angeles, CA USA
Giza, Christopher
Fanselow, Michael
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Univ Calif Los Angeles, Psychol, Los Angeles, CA USA
Univ Calif Los Angeles, Staglin Ctr Brain & Behav Hlth, Los Angeles, CA USAUniv Calif Los Angeles, Neurosurg, Los Angeles, CA USA
机构:
Univ Toronto, St Michaels Hosp, Inst Med Sci, Cara Phelan Ctr Trauma Res, Toronto, ON M5B 1W8, CanadaUniv Toronto, St Michaels Hosp, Inst Med Sci, Cara Phelan Ctr Trauma Res, Toronto, ON M5B 1W8, Canada
Park, E
Baker, AJ
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Univ Toronto, St Michaels Hosp, Inst Med Sci, Cara Phelan Ctr Trauma Res, Toronto, ON M5B 1W8, CanadaUniv Toronto, St Michaels Hosp, Inst Med Sci, Cara Phelan Ctr Trauma Res, Toronto, ON M5B 1W8, Canada