Neuronal Cell Death in Hippocampus Induced by Homocysteic Acid in Immature Rats

• Published in: Epilepsia (Copenhagen) Vol. 44; no. 3; pp. 299 - 304
• Main Authors: Langmeier, Miloš, Folbergrová, Jaroslava, Haugvicová, Renata, Pokorný, Jaroslav, Mareš, Pavel
• Format: Journal Article
• Language: English
• Published: Boston, MA, USA Blackwell Science Inc 01.03.2003; Blackwell
• Subjects: Animals; Animals, Newborn; Apoptosis - physiology; Biological and medical sciences; Cell Count; Cell degeneration; Cell Nucleus - pathology; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - pathology; Dentate Gyrus - cytology; Dentate Gyrus - drug effects; Dentate Gyrus - pathology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - pathology; Homocysteic acid; Homocysteine - analogs & derivatives; Homocysteine - pharmacology; Immature rats; Male; Medical sciences; Nerve Degeneration - pathology; Nervous system (semeiology, syndromes); Neuroglia - cytology; Neuroglia - pathology; Neurology; Neurons - cytology; Neurons - drug effects; Neurons - pathology; Nuclear fragmentation; Pyramidal Cells - cytology; Pyramidal Cells - pathology; Rats; Rats, Wistar; Seizures; Seizures - chemically induced; Seizures - pathology; Animal model; Nervous system diseases; Cerebral cortex; Pathophysiology; Rat; Epilepsy; Rodentia; Homocysteic acid-Immature rats- Seizures-Cell degeneration-Nuclear fragmentation; Cerebral disorder; Vertebrata; Experimental disease; Mammalia; Cell death; Newborn animal; Morphology; Central nervous system disease; Hippocampus; Brain (vertebrata)
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1046/j.1528-1157.2003.31702.x

Purpose: To examine the morphologic alterations in the cerebral cortex and hippocampus of immature rats 6 days after the generalized clonic–tonic seizures induced by homocysteic acid (HCA). Methods: Seizures were induced by bilateral intracerebroventricular infusion of HCA (600 nmol per each side) in 12‐day‐old rats. After 6 days, rat pups were transcardially perfused under deep ether anesthesia with heparinized normal saline and subsequently with the fixation solution (4% paraformaldehyde in phosphate buffer, pH 7.4, for light microscopy) or with Karnovsky's solution (4% paraformaldehyde and 2% glutaraldehyde in phosphate buffer, pH 7.4, for electron microscopic analysis). Nissl stain and the DNA‐specific dye bis‐benzimide (Hoechst 33342) were used. Results: No pathologic changes were found in the cerebral cortex, whereas serious alterations occurred in the hippocampus. A total loss of CA3 pyramidal cells was observed, with marked changes in the CA1 region and dentate gyrus. A prominent glial reaction was seen in many regions of the hippocampal formation. A slight dilatation of the cerebral ventricles was noticed in some experimental as well as control animals. In the granule cell layer of the dentate gyrus, neurons with segmented or fragmented nuclei in various stages of degeneration were detected, displaying the features of apoptotic death. Conclusions: These findings demonstrate the vulnerability of the immature rat brain, which most likely reflects both the direct neurotoxic effect of HCA and prolonged seizure activity. The relative contribution of these two factors still remains to be assessed.