Much evidence shows that glia regulates the
cation and
anion content of brain interstitial space. In rats the pH and
bicarbonate (HCO3-) concentration of neurons and glia were derived from
carbon 14-labeled HCO3- and
dimethyloxazolidinedione uptake into brain and cerebrospinal fluid.
Acetazolamide increases the total CO2 concentration in neurons and decreases the pH and HCO3- concentration in glia. Inhibition of glial
carbonic anhydrase (CA) reduces conversion of neuronally derived CO2 to HCO3-, glial pH is lowered, and neuronal CO2 accumulates. CA therefore has an essential role in regulating pH in neurons, glia, and interstitial fluid. In audiogenic seizure mice, glial CA activity is increased and glial
anion transport is reduced. As the mice age, seizure susceptibility, the increased CA activity, and the defect in
anion transport disappear concurrently. The enhanced CA activity in the glial cells of these mice is an adaptive mechanism to overcome the defect in
anion transport that results from a deficiency of HCO3- -dependent and Na+- and K+ -dependent
adenosine triphosphatase.
Pentylenetetrazol stimulates neurons in neonatal rats, but after 10 days of age, when glia is present, it too is stimulated and the
seizures are attenuated.
Cobalt implantation in the cortex of rats also induces a glial response that ameliorates the
focal seizures produced by this procedure.