Purkinje cell vulnerability to mild traumatic brain injury.
In this study we examined the cerebellar response to mild traumatic brain injury by assessing microglial activation and Purkinje cell loss. Activated microglia were identified using the antibodies OX-42 and ED-1 as well as isolectin B4. The anti-Purkinje cell antibody PEP-19 was used to evaluate Purkinje cell loss after injury. The mechanism of cell injury was examined using a monoclonal antibody to the inducible 72-kDa heat shock protein. A monoclonal antibody to the N-terminal sequence of Fos was used as a marker for neuronal activation. There was progressive activation of microglia in the cerebellar vermis within a few days after forebrain injury. In coronal sections the processes of activated microglia were oriented in "stripes" perpendicular to the cortical surface. In sagittal sections the activated microglia were in irregularly shaped clusters or in a fan-like distribution that radiated from the Purkinje cell layer toward the cortical surface. There was a significant loss of Purkinje cells 7 days postinjury as compared to the control group. There was no evidence of induction of heat shock protein in the cerebellum. In addition, there was no evidence of induction of c-Fos protein in either the cerebellar cortex or inferior olivary nuclei within the first 3 h after injury. These studies demonstrate that a fluid percussive impact to the forebrain results in cerebellar damage. The close anatomical association between activated microglia and Purkinje cells suggests that Purkinje cell injury is the cause of the microglial activation. The mechanism of Purkinje cell death, however, remains unclear.
Fukuda
K
K
Department of Neurosurgery, University of California, San Fracisco General Hospital, USA.
Aihara
N
N
Sagar
S M
SM
Sharp
F R
FR
Pitts
L H
LH
Honkaniemi
J
J
Noble
L J
LJ
D000818:Animals; D000911:Antibodies, Monoclonal; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry; D037102:Lectins; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D018840:HSP70 Heat-Shock Proteins; D037102:Lectins; D016760:Proto-Oncogene Proteins c-fos