Neuronal lesions in mercaptopropionic acid-induced status epilepticus

Abstract

Neuropathological studies of rats were made after seizures of different durations. Seizures were produced by mercaptopropionic acid in paralyzed, ventilated rats that were perfusion-fixed immediately (acute) or after 2-7 days of recovery (chronic). Analysis of chronic rats, which had only 20-min seizures, showed that damage occurred to several structures including: the substantia nigra pars reticulata, the hypothalamus, the diagonal band of Broca, and the globus pallidus; the damage was worse with longer seizures. In rats perfused acutely no changes were detected in paraffin sections in the aforementioned structures if the length of seizures was 45 min or less. It was concluded that: (1) mercaptopropionic acid-induced seizures cause permanent lesions to specific brain areas, with the most pronounced effect in the substantia nigra pars reticulata; (2) the lesions result from the seizures, and they are roughly proportional to the seizures duration; and (3) permanent lesions may begin within 20 min but require longer times to become visible on light microscopy.

Effect of Status Epilepticus on Hypoxic-Ischemic Brain Damage in the Immature Rat

“…Survivors were reared with their dams until 30 d of postnatal age, after which their brains were analyzed for the presence and extent of brain damage. As in the previous investigations (see above), there was no statistically significant difference between the In adult rats, status epilepticus readily leads to brain damage (8,10,20). In contrast, immature rats appear resistant to the brain damaging effect of status epilepticus.…”

“…Prolonged seizures or status epilepticus lead to brain damage in adult animals, with morphologic alterations in selectively vulnerable structures; especially the cerebral cortex, hippocampus. and substantia nigra (7)(8)(9)(10). On the othe~.…”

“…On the othe~. hand, both published and unpublished experimental studies in immature animals of most, although not all, species have failed to demonstrate that even prolonged seizures (status epilepticus) lead to overt brain injury (1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14] (see "Discussion").…”

Systemic Effects of Generalized Convulsive Status Epilepticus

“…inhibitor 3-mercaptopropionic acid (OConnell et al, 1988;Towfighi et al, 1989) in rats. The challenge facing contemporary investigators is to demonstrate what contribution, if any, systemic physiologic alterations make to the neuropathologic sequelae seen following SE.…”

“…The dur ration of the post-SE recovery time allowed before the brain is perfusion-fixed has varied widely among published experimental reports. Because both the location and severity of neuropathology following SE changes with the recovery time (Griffiths et al, 1984;OConnell et al, 1988), it is essential that this factor be considered when evaluating neuropathologic studies. One of the significant challenges that investigators face in doing this type of experimental study is the difficulty of maintaining animals in good health during and after prolonged episodes of SE.…”