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Research Interests

There are over 1 million new cases of head injury annually in North America, of which, approximately 80,000 result in permanent disabilities. Unfortunately, there are no clinically effective pharmacological treatments that are known to reduce the pathological effects of brain injury and enhance recovery of motor and cognitive function. This research investigation will identify some of the mechanisms that are involved in recovery of motor and cognitive function following brain injury. We know that patients with brain injury exhibit some degrees of recovery, however, information regarding these processes are virtually unknown. Our preliminary data support the idea that administration of growth factors has a significant effect on brain cell repair and recovery of motor function after brain injury. Information regarding the mechanisms of action of growth factors in activation of recovery processes will help us to understand how the brain repairs itself after injury.

Research in the area of Traumatic Brain Injury (TBI) represents a new initiative in my laboratory. Funding from The Nova Scotia Neurotrauma Society (limited 1 year grants) has allowed us to develop a simple but highly reproducible weight drop model of TBI. Using the weight drop model of TBI, we have characterized motor function deficits after TBI to the dorsal motor cortex and correlated the motor function deficits with the temporal and spatial changes in heat shock protein induction and reactive gliosis (see Allen et al., 2000, Neuroscience). In addition, we have also identified an important phenomena that occurs following repeated mild brain injury. Our studies have demonstrated that repeated mild TBI to the same site in the dorsal motor cortex prior to a a subsequent severe TBI to the same site conditions the brain so that there is no motor function deficit even though the hindlimb region of the motor cortex is completely destroyed by the severe TBI. These data do not demonstrate that repeated mild TBI is neuroprotective but

rather that certain types of mild cortical injury elicits enough damage to trigger a "compensatory mechanism" that allows a secondary hindlimb motor function site to be recruited so that subsequent injury to the primary motor cortex has little or no effect on hindlimb motor function (Allen et al., 2000, Neuroscience). Our data on heat shock protein induction after TBI has indicated regions of the brain that may be involved in spontaneous recovery of motor function after brain injury.



Our interest in the role of the cerebellum in recovery of motor function after cerebral cortical injury has promoted us to carry our a detailed study of the effects of cerebellar injury on motor function and heat shock protein induction. This study has identified a region of the cerbellar cortex (paravermal/lateral area) that has profound effects on hindlimb motor function after weight drop injury. We have also characterized the induction of both Hsp70/72 and Hsp25/27 in the cerebellum after injury and correlated these findings with that of the motor behavior. More importantly, we have identified a survival time period after focal brain injury where Hp25/27 is induced in Purkinje cells as well as
Bergmann glial cells and other types of glial cells. This is the first time that Hsp25/27 has been observed in Purkinje cells after any type of ischemic or traumatic insult (Allen and Chase, Neuroscience 2001. Further studies are required to characterize the effects of TBI on other regions of the cerebellar cortex and deep cerebellar nuclei and to determine the role of the cerebellum in the spontaneous recovery of motor function after brain injury (see present proposal). In addition, we have also noted profound changes in calcium binding protein production after TBI to the cerebellar cortex. Our investigations have characterized the effects of focal injury to the cerebellum and demonstrated that many of the Purkinje cells that are immunoreactive for Hsp25/27 after injury are also calbindin or parvalbumin immunoreactive (Cerebellum, 2002, in press). Although the role of calcium binding protein induction in Purkinje cells is unknown, studies of the effects of repeated mild TBI to the cerebellar cortex on calcium binding proteins may help us to understand the effects of focal injury on neuronal function and recovery processes.