Perinatal hypoxic ischemic encephalopathy affects the proportion of GABA-immunoreactive neurons in the cerebral cortex of the rat.

The hypothesis was tested whether perinatal hypoxic ischemia leads to a preferential degeneration of the GABAergic inhibitory neurons in the cerebral cortex which, in turn, could account for the reported higher risk of developing epilepsy later in life. To that end rat pups, aged 12-13 days, were made hypoxic by employing a combination of unilateral ligation of one of the carotid arteries and a 90-min exposure to 8% O2. After recovery periods of 3, 7, 35 and 150 days, the animals were sacrificed by perfusion fixation and the brains embedded in Epon. Transverse semi-thin sections were alternately stained with an antibody against GABA and with Toluidine blue. By using an unbiased morphometric method (the disector) the number of GABA-immunoreactive (GABA-IR) neurons and the total number of nerve cells per unit volume of tissue were estimated in corresponding neocortical areas in the ipsilateral (damaged) and contralateral ('control') hemisphere. For all animals with post-ischemic survival times of 3 and 7 days GABA-IR cells constituted a lower proportion of the total number of nerve cells in the damaged than in the 'control' cortical areas. This finding was consistent with the outcome of an earlier in vitro study. By contrast, in all animals with a survival time of 35 and 150 days, the proportion of GABA-IR neurons was higher on the damaged than on the 'control' side. This switch in the direction of the left/right differences, apparently depending on the length of the post-ischemic survival time, was statistically significant. No lateralization in the proportion of GABA-IR cells was detected in the cerebral cortex of the control rats. These observations, therefore, do not support the hypothesis that perinatal hypoxic ischemia ultimately leads to a preferential loss of GABAergic neurons in the cerebral cortex.

The influence of nifedipine and mioflazine on mitochondrial calcium overload in normoxic and ischaemic guinea-pig hearts.

The influence of nifedipine (20 nM) and mioflazine (300 nM), i.e. concentrations inducing a 60-70% recovery of cardiac function during reperfusion of globally ischaemic guinea-pig working hearts, on the mitochondrial calcium content was investigated in normoxic, globally ischaemic and reperfused globally ischaemic guinea-pig working hearts. Mitochondrial calcium was determined electronmicroscopically with oxalate-pyroantimonate method. In normoxic hearts both nifedipine and mioflazine reduced the mitochondrial calcium content. Global ischaemia for 45 min and subsequent reperfusion for 25 min resulted in a pronounced mitochondrial calcium overload and damage to the cellular structure. In ischaemic and in reperfusion hearts the drugs maintained mitochondrial calcium at pre-ischaemic levels and decreased the damage to the cellular structure.