Neocortical GABA release at high intracellular sodium and low extracellular calcium: an anti-seizure mechanism.

In epilepsy, the GABA and glutamate balance may be disrupted and a transient decrease in extracellular calcium occurs before and during a seizure. Flow Cytometry based fluorescence activated particle sorting experiments quantified synaptosomes from human neocortical tissue, from both epileptic and non-epileptic patients (27.7% vs. 36.9% GABAergic synaptosomes, respectively). Transporter-mediated release of GABA in human and rat neocortical synaptosomes was measured using the superfusion technique for the measurement of endogenous GABA. GABA release was evoked by either a sodium channel activator or a sodium/potassium-ATPase inhibitor when exocytosis was possible or prevented, and when the sodium/calcium exchanger was active or inhibited. The transporter-mediated release of GABA is because of elevated intracellular sodium. A reduction in the extracellular calcium increased this release (in both non-epileptic and epileptic, except Rasmussen encephalitis, synaptosomes). The inverse was seen during calcium doubling. In humans, GABA release was not affected by exocytosis inhibition, that is, it was solely transporter-mediated. However, in rat synaptosomes, an increase in GABA release at zero calcium was only exhibited when the exocytosis was prevented. The absence of calcium amplified the sodium/calcium exchanger activity, leading to elevated intracellular sodium, which, together with the stimulation-evoked intracellular sodium increment, enhanced GABA transporter reversal. Sodium/calcium exchange inhibitors diminished GABA release. Thus, an important seizure-induced extracellular calcium reduction might trigger a transporter- and sodium/calcium exchanger-related anti-seizure mechanism by augmenting transporter-mediated GABA release, a mechanism absent in rats. Uniquely, the additional increase in GABA release because of calcium-withdrawal dwindled during the course of illness in Rasmussen encephalitis. Seizures cause high Na(+) influx through action potentials. A transient decrease in [Ca(2+)]e (seizure condition) increases GABA transporter (GAT)-mediated GABA release because of elevated [Na(+)]i. This amplifies the Sodium-Calcium-Exchanger (NCX) activity, further increasing [Na(+)]i and GABA release. The reduction in [Ca(2+)]e triggers a GAT-NCX related anti-seizure mechanism by augmenting GAT-mediated GABA release. This mechanism, obvious in humans, is absent in rats.

Decompressive craniectomy after severe traumatic brain injury in children: complications and outcome.

Decompressive craniectomy (DC) is a controversially discussed neurosurgical procedure to reduce elevated intracranial pressure after severe traumatic brain injury (TBI). In contrast to adults, several studies could show a benefit for the pediatric population, but still DC is considered as an emergency procedure only. The aim of our study was to identify secondary complications and long-term sequelae of the procedure. All children presenting to the University Medical Center Freiburg between 2005 and 2013 who underwent DC after severe TBI were retrospectively reviewed with respect to complications and outcome. Twelve children were included with a mean Glasgow Coma Scale of 4.5 ± 1.7. The most frequent complications after TBI and DC were formation of hygroma (83%), aseptic bone resorption of the reimplanted bone flap (50%), posttraumatic hydrocephalus (42%), secondary infection or dysfunction of ventriculoperitoneal shunt (25%) or cranioplasty (33%), and epilepsy (33%). Because of these complications, 75% of patients required further surgery in addition to cranioplasty with up to eight interventions. At follow-up, mean Glasgow Outcome Scale was 3.3 ± 1.2. Within our patient population, we demonstrated high incidence of complications after DC, leading to further surgical procedures and longer hospitalization. These potential complications have to be considered in any decision about DC as an emergency procedure.

Altered transporter-mediated neocortical GABA release in Rasmussen encephalitis.

To learn whether epileptic seizures in Rasmussen encephalitis (RE) may be promoted by insufficient γ-aminobutyric acid (GABA) release. (3) H-GABA was released from neocortical synaptosomes through transporter reversal following intrasynaptosomal Na(+) accumulation by veratridine that prevents inactivation of Na(+) channels. Tissues of three RE patients were compared with those of nine non-RE. In RE, the release was markedly reduced. In non-RE, the extracellular Ca(2+) concentration ([Ca(2+) ]e ) was inversely related to the amount of release. In RE, the percental decline of additional release upon Cae 2+ withdrawal was linked with the presurgical duration of epilepsy. Permanent opening of Na(+) channels by veratridine resembles maximal frequency of action potentials corresponding to epileptic seizures. These are preceded by a fall in [Ca(2+) ]e . Zero [Ca(2+) ]e increased release through the Na(+) /Ca(2+) exchanger additionally elevating intrasynaptosomal Na(+) . This enhanced GABA release probably reflects an antiseizure mechanism. In RE, the additional release gets lost over epilepsy duration.