Experimental neurology
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Experimental neurology · Apr 1994
Distribution of forebrain diffuse axonal injury following inertial closed head injury in miniature swine.
Diffuse axonal injury (DAI) is one of the most frequently encountered types of brain damage resulting from closed head injury. This study was designed to verify whether DAI could be produced in miniature swine by rapid acceleration and deceleration of the head in the coronal plane. Hanford miniature swine (16-19 kg) were anesthetized with 3% isoflurane and their heads accelerated rapidly once through a 60-105 degrees arc in the coronal plane, producing only transient post-traumatic unconsciousness without prolonged coma. ⋯ In 9 of 12 animals, lesions characterized by foci of SMI-32 positive axonal retraction balls were present at the white matter/gray matter junction at the crests of gyri in the dorsolateral regions of the frontal, parietal, and temporal cortices and along margins of the lateral ventricles. A high density of pyramidal neuron perikarya in layers III and V within cortical gyri associated with subcortical DAI were intensely positive for SMI-31 immunohistochemistry. These results validate the use of miniature swine in studies of axonal injury and demonstrate that axonal injury analogous to that seen in the mildest form of DAI (grade I) can be produced in these animals without producing prolonged coma.
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Experimental neurology · Apr 1994
Blockade of GABA uptake with tiagabine inhibits audiogenic seizures and reduces neuronal firing in the inferior colliculus of the genetically epilepsy-prone rat.
Tiagabine is a new anticonvulsant drug that blocks the uptake of GABA, prolonging the action of this inhibitory transmitter. In the present study the effects of systemically administered tiagabine [30 mg/kg, ip (ED50)] were examined on audiogenic seizure (AGS) severity and neuronal firing in the inferior colliculus (IC) in the freely moving genetically epilepsy-prone rat (GEPR-9). The IC is known to be critical to AGS initiation. ⋯ The time course of the reduction in neuronal firing of IC neurons paralleled the reduction in seizure severity. Previous studies have shown that two forms of GABA-mediated inhibition (intensity-induced and offset inhibition) in IC neurons are most prominent at high stimulus intensities, which are required to induce AGS. The blockade of GABA uptake by tiagabine may act to inhibit audiogenic seizures, in part, by intensifying these naturally occurring forms of acoustically evoked inhibition in inferior colliculus neurons.