Abstracts

Following severe rostral parasaggital fluid percussion injury (rpFPI) in the rat, the frontal parietal cortex develops into an epileptic focus¹. To begin the identification of the epileptogenic mechanisms we have examined the time course of changes in glial electrophysiology. Severe rpFPI was induced in 5 week old Sprague-Dawley male rats (3.25-3.5 atm). Coronal slices were obtained from ipsilateral hemispheres 1 day and 1 month post-surgery in FPI and sham-injured animals. Whole-cell (WC) patch clamp recordings were obtained from macroglia residing at and around the injury site (bregma 0mm - -3.5 mm) in layers IV-VI of the frontal parietal cortex and in the CA3 region of the hippocampus. Bath application of 40 [mu]M Ba²⁺ was used to block K[sub]IR[/sub] channels. All recordings were performed at 35^oC. K[sub]IR[/sub] activity is expressed as percentage of the whole cell current blocked in the presence of extracellular Ba²⁺. Data are shown as means [plusmn] SEM. Statistics with Mann-Whitney U test, unless otherwise noted. K[sub]IR[/sub] currents were significantly depressed after injury from 15.5[plusmn]1.9% (n=7) of the WC current to 6.6[plusmn]1.1% (n=6) in neocortical glia (p[lt]0.005), and from 19.8[plusmn]2.2% (n=10) to 12.4[plusmn]1.7% (n=8) in hippocampal glia (p[lt]0.05). Conversely, K[sub]IR[/sub] currents recovered by 1 month post-injury, from 19.6[plusmn]1.5% (n=9) to 13.5[plusmn]2.7% (n=9) in FPI neocortex, and from 18.1[plusmn]2.3% (n=12) to 16.8[plusmn]5.3% (n=6) in FPI hippocampus. A significantly greater span of K[sub]IR[/sub] currents was found in injured slices one month post-injury (Moses test; p[lt] 0.05), suggesting the persistence of a functionally compromised subpopulation of glia. Also, cells exhibiting an outwardly rectifying current profile, characteristic of dividing or reactive glia, were rare in normal tissue (1%) and became more frequent (11%) at 1 month postinjury (Chi²; p[lt]0.02). These data confirm and expand our original observation of impaired glial K⁺ buffering acutely after midline FPI ². K[sub]IR[/sub] conductance is decreased in both neocortical and hippocampal glia 1 day after rpFPI, and it partially recovers by 1 month post-injury. A subpopulation of glia with abnormally low K[sub]IR[/sub] conductance persists over time. K[sub]IR[/sub] channels are known to contribute importantly to the maintenance of extracellular K⁺ homeostasis, and their blockade results in pro-epileptic elevation of extracellular K⁺. These data point to a possible role for glia in FPI-induced epilepsy.
1) D[apos]Ambrosio, Fairbanks, Fender, Doyle, Born, Miller (2003) Posttraumatic epilepsy following fluid percussion injury in the rat. Brain. 2003 Nov 7 [Epub ahead of print]. Brain, 2004, 127(Pt 2):304-14.
2) D[apos]Ambrosio R, Maris DO, Grady MS, Winn HR, Janigro D (1999) Impaired K(+) homeostasis and altered electrophysiological properties of post-traumatic hippocampal glia. J Neurosci. 19(18):8152-62. (Supported by NS040823 to RD.)