Effects of kindled seizures upon hematopoiesis in rats.
OBJECTIVE
Studies conducted in epilepsy patients and experimental animals have suggested a linkage between seizure activity and alterations in immune functions. However, little is known about the underlying mechanisms. The present study sought to determine whether chronic seizures result in changes in hematopoietic functions that contribute to alterations in immune function.


METHODS
Sprague-Dawley rats were implanted with electrodes in the basal amygdala or frontal cortex for induction of focal seizures by kindling. After inducing stage 5 seizures for 30 days, rats were sacrificed and assays for colony-forming units granulocyte/macrophage (CFU-GM) were performed to study progenitor cell functions. Long-term culture-initiating culture (LTC-IC) assays were employed to determine the effects of kindling upon bone marrow stroma. A Western blot for caspase-3 and CFU-GM assays from peripheral blood were used to determine the cause of reduced cellularity of bone marrow.


RESULTS
Kindled seizures of the basal amygdala resulted in decreases in bone marrow cellularity and hyperproliferation of colony-forming cells in peripheral blood and bone marrow. Modified LTC-IC assays, where co-cultures of bone marrow cells and stroma from experimental animals were employed, revealed that hyperproliferation of progenitor cells was not associated with alterations in stromal functions. The changes observed in this study were associated with seizure foci in the basal amygdaloid complex but not the frontal cortex.


CONCLUSIONS
Kindled seizures of the basal amygdala induce hyperproliferation of bone marrow progenitor cells, suggesting that alterations in immunological functions observed following seizure activity may be due to changes in hematopoietic functions. Such changes appear to be site specific within the brain.
Bhatt
Rekha
R
Department of Neurosciences, MSB, H-512, University of Medicine and Dentistry, Newark, NJ 07104, USA.
Rameshwar
Pranela
P
Goldstein
Kenneth
K
Siegel
Allan
A
D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000473:pathology / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002455:Cell Division / Q000502:physiology; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D005260:Female; D005269:Femur; D006410:Hematopoiesis / Q000502:physiology; D007696:Kindling, Neurologic / Q000502:physiology*; D007958:Leukocyte Count; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000097:blood* / Q000201:enzymology / Q000503:physiopathology*; D013234:Stem Cells / Q000473:pathology / Q000502:physiology
C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases