Oxygen and glucose deprivation induces major dysfunction in the somatosensory cortex of the newborn rat.
The mechanisms and functional consequences of ischemia-induced injury during perinatal development are poorly understood. Subplate neurons (SPn) play a central role in early cortical development and a pathophysiological impairment of these neurons may have long-term detrimental effects on cortical function. The acute and long-term consequences of combined oxygen and glucose deprivation (OGD) were investigated in SPn and compared with OGD-induced dysfunction of immature layer V pyramidal cortical neurons (PCn) in somatosensory cortical slices from postnatal day (P)0-4 rats. OGD for 50 min followed by a 10-24-h period of normal oxygenation and glucose supply in vitro or in culture led to pronounced caspase-3-dependent apoptotic cell death in all cortical layers. Whole-cell patch-clamp recordings revealed that the majority of SPn and PCn responded to OGD with an initial long-lasting ischemic hyperpolarization accompanied by a decrease in input resistance (R(in)), followed by an ischemic depolarization (ID). Upon reoxygenation and glucose supply, the recovery of the membrane potential and R(in) was followed by a Na+/K+-ATPase-dependent postischemic hyperpolarization, and in almost half of the investigated SPn and PCn by a postischemic depolarization. Whereas neither a moderate (2.5 mm) nor a high (4.8 mm) increase in extracellular magnesium concentration protected the SPn from OGD-induced dysfunction, blockade of NMDA receptors with MK-801 led to a significant delay and decrease of the ID. Our data demonstrate that OGD induces apoptosis and a profound dysfunction in SPn and PCn, and underline the critical role of NMDA receptors in early ischemia-induced neuronal damage.
Albrecht
Juliane
J
Institute of Physiology & Pathophysiology, Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
Hanganu
Ileana L
IL
Heck
Nicolas
N
Luhmann
Heiko J
HJ
D000818:Animals; D000831:Animals, Newborn; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D013003:Somatosensory Cortex / Q000473:pathology / Q000503:physiopathology*; D014044:Tolbutamide / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D010042:Ouabain; D016291:Dizocilpine Maleate; D014044:Tolbutamide; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D008274:Magnesium; D005947:Glucose