title: Structural and functional alterations of cerebellum following fluid percussion injury in rats.
abstract: 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 beta-amyloid precursor protein (betaAPP) 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.
authors.affiliation: Traumatic Brain Injury Laboratory, Cara Phelan Centre for Trauma Research, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada M5B 1W8. aij@smh.toronto.on.ca
authors.forename: Jinglu
authors.initials: J
authors.lastname: Ai
authors.forename: Elaine
authors.initials: E
authors.lastname: Liu
authors.forename: Eugene
authors.initials: E
authors.lastname: Park
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Baker
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000502:physiology; D002531:Cerebellum / Q000293:injuries* / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000473:pathology; D004558:Electric Stimulation; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D011689:Purkinje Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides