Seizure induced gliogenesis in the piriform cortex.
Published: 2004
Language: eng
Number of pages: 202
Description: Complex partial epilepsy is a seizure disorder in which attacks frequently arise from foci located in the temporal lobes. The amygdala-kindling model is a widely used model of complex partial epilepsy with secondary generalization. The present study was designed to (1) quantitatively assess astrocytic changes in the rat piriform cortex in the amygdala-kindling model of epilepsy. (2) to assess the functional role of astrocytic proliferation in the kindling process. In the fully kindled subjects, once the experimental subjects reached five stage 5 seizures, stimulation was stopped, and subjects were allowed to survive for the interval appropriate to their group (7, 18, 30, or 90 days). Following each interval, the kindled and control animals in that group were given BrdU injections and sacrificed 24h following the last injection. A significantly higher number of dividing astrocytes (identified by co-labeling with antibodies to bromodeoxyuridine and to one of the astrocytic intermediate filament proteins glial fibrillary acidic protein or vimentin) was found in both partially kindled (Stage 1) and fully kindled (Stage 5) brains.The second part of this project involved the selective elimination of astrocytes both in the ipsi- or contralateral side to the stimulation site. This was achieved through intracerebral injections of the astrotoxins alpha-aminoadipic acid or fluorocitrate. Both D and L isomers of alpha-AA were tested to examine the gliotoxicity of each isomer. It was found that L-alphaAA is the active isomer since the D-isomer did not yield any positive result. In addition to the focal elimination of astrocytes at the stimulation site, L-alphaAA infusions also significantly reduced the proliferating astrocytes in the piriform cortex. In addition, the astrocytic loss significantly raised the afterdischarge threshold, lowered the afterdischarge duration (spiking), and dramatically reduced the motor seizure intensity. Likewise, infusions of fluorocitrate had anti-kindling effects. During this period, the thresholds were dramatically increased, followed by the retardation of kindling. These results suggest that gliogenesis in response to kindling stimulations, are involved in both the development and maintenance of the seizure-prone state, and therefore might be epileptogenic.
Notes: Adviser:  W. M. Burnham.

Thesis (Ph.D.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Dissertation Abstracts International, Volume: 65-10, Section: B, page: 5019.