The development of changes in hippocampal GABA immunoreactivity in the rat kindling model of epilepsy: A light microscopic study with gaba antibodies

Abstract

Immunocytochemical techniques were used to study changes of GABA immunoreactivity in the rat hippocampal CA1 region during kindling epileptogenesis, gradually developing over a period of two weeks by daily electrical tetanization of Schaffer collaterals/commissural fibres. The number of GABA-immunoreactive somata per mm 2 was quantified in CA1 region after 6 and 14 stimulus-induced afterdischarges and in fully kindled animals. The absolute values were compared with those obtained from controls and the relative difference between the side where the stimulations were applied and the contralateral side was determined. In comparison to controls the rats showed, after 6 afterdischarges at the ipsilateral, stimulated side, a slight increase in cell density of about 10%; after 14 afterdischarges, there was a significant increase of 38% together with an enhanced labelling density, while in fully kindled rats (34 afterdischarges) there was no significant difference with controls. At the contralateral side, we observed a different pattern of, respectively, a small decrease (17%), no significant difference, and a significant increase of 22% in fully kindled animals. This result is discussed in relation to observations that fully kindled rats, investigated 24 days after the last seizure of the acquisition phase, showed rather a significant decrease by 35% of cell density at the stimulated side and a regional loss of immunoreactivity of varicosities. At this point in time, no significant changes were found at the contralateral side. The complex time-course of GABA immunoreactivity during epileptogenesis consists of a transient increase in the early phase of kindling acquisition followed by a process of gradual reduction that leads to the long-term decrease of GABA immunoreactivity and high excitability.