The purpose of this proposal is to consider those neural and vascular events which occur in minor brain injury and as such, the specific aims of this proposal are (1) to determine the initial post-traumatic axonal changes which are associated with the onset of the genesis of reactive axonal swellings (2) to follow the long term fate of the traumatically induced reactive axonal swellings to determine if they undergo degenerative change or rather do they initiate regenerative axonal sprouting and (3) to address the role of catecholamine-laden subarachnoid hemorrhage in the induction of those permeability and blood flow alterations commonly seen subsequent to mechanical brain injury. To explore the issue of traumatically induced axonal change, anterograde peroxidase passage visualized with tetramethylbenzidine, and cobalt-glucose oxidase procedures will be analyzed at the light microscopic (LM) and transmission electron microscopic (TEM) levels following the induction of the mechanical brain injury. Alterations in the intra-axonal peroxidase profile coupled with any alterations in the axon cylinder will be analyzed during the first hour following the traumatic event to determine whether frank axonal tearing or more subtle axonal abnormalities are initiated by the traumatic episode. Additionally, peroxidase-laden reactive swellings will be followed over a several week course to determine via LM and TEM analyses if such reactive swellings can give rise to regenerative sprouts, which ultimately extend through the substance of the unaltered brain parenchyma. For the purpose of considering the vascular influences of traumatic subarachnoid hemorrhage, catecholamine-laden blood, harvested from traumatized animals will be infused into non-traumatized animals under isobaric conditions. Via the use of intravascular horseradish peroxidase (HRP) and radiolabeled microspheres, vascular permeability to HRP and regional cerebral blood flow will be assessed over a four hour course. Brain samples harvested for such blood flow analyses will also be studied via LM, TEM and scanning electron microscopic analyses to determine if this infusion of blood causes vascular alteration. Additionally to glean a more focal analysis of any flow abnormalities, HRP and iodo (14C) antipyrine studies will also be conducted. As these phenomena cannot be investigated in man, their consideration in animal models provides the most rational approach for obtaining an enhanced understanding of those events involved in brain injury.
Showing the most recent 10 out of 62 publications
