[Show abstract][Hide abstract] ABSTRACT: Seizures represent a common and serious complication of hypoglycemia. Here we studied mechanisms of control of hypoglycemic seizures induced by insulin injection in fasted and nonfasted rats. We demonstrate that fasting predisposes rats to more rapid and consistent development of hypoglycemic seizures. However, the fasting-induced decrease in baseline blood glucose concentration cannot account for the earlier onset of seizures in fasted versus nonfasted rats. Data obtained with c-Fos immunohistochemistry and [14C]2-deoxyglucose uptake implicate a prominent involvement of the substantia nigra reticulata (SNR) among other structures in the hypoglycemic seizure control. This is supported by data showing that fasting decreases the SNR expression of K(ATP) channels, which link metabolism with activity, and is further confirmed with microinfusions of K(ATP) channel agonist and antagonist. Data obtained with whole-cell and perforated patch recordings from SNR neurons in slices in vitro demonstrate that both presynaptic and postsynaptic K(ATP) channels participate in the failure of the SNR to control hypoglycemic seizures. The results suggest that fasting and insulin-induced hypoglycemia can lead to impairment in the function of the SNR, leading thus to hypoglycemic seizures.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 10/2008; 28(38):9349-62. DOI:10.1523/JNEUROSCI.3195-08.2008 · 6.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neurological complications of hypoglycemia often include seizures and fasting is a predisposing factor for seizures to occur. The mechanisms involved are unknown. In rats, insulin administration induces hypoglycemia, which may lead to generalized seizures with barrel rotations as a hallmark. Here we compared the incidence of barrel rotations in fasted and nonfasted rats. Further, we investigated the role of the substantia nigra pars reticulata (SNR) in control of barrel rotations using localized bilateral microinfusions of GABA(A) or GABA(B) receptor agonists (muscimol or baclofen, respectively) or an N-methyl-D-aspartate (NMDA) receptor antagonist (AP7). The incidence of barrel rotations was significantly higher in fasted compared to nonfasted rats. SNR infusions of muscimol were ineffective, while both baclofen and AP7 significantly decreased occurrence of barrel rotations. These data suggest that during hypoglycemia, the SNR seizure controlling system has different properties than in seizure models not involving a metabolic stress.