Bone marrow mononuclear cells reduce seizure frequency and improve cognitive outcome in chronic epileptic rats

• Published in: Life sciences (1973) 2011-08, Vol.89 (7-8), p.229-234
• Main Authors: Venturin, Gianina Teribele, Greggio, Samuel, Marinowic, Daniel Rodrigo, Zanirati, Gabriele, Cammarota, Martín, Machado, Denise Cantarelli, DaCosta, Jaderson Costa
• Format: Article
• Language: English
• Subjects: Animals; Bone marrow; Bone Marrow Cells - cytology; Bone marrow stem cells; Brain; Cell Transplantation; Chronic Disease; Cognition; Cognition Disorders - chemically induced; Cognition Disorders - prevention & control; Cognitive ability; Data processing; Diazepam; Diazepam - pharmacology; disease course; Disease Models, Animal; drug therapy; Epilepsy; Epilepsy - complications; Epilepsy - therapy; Excitability; Fibroblasts; genetically modified organisms; Green fluorescent protein; intravenous injection; Leukocytes (mononuclear); Lithium - pharmacology; Male; Maze Learning - drug effects; memory; Memory Disorders - chemically induced; Memory Disorders - prevention & control; Mice; Mice, Inbred C57BL; Monocytes - cytology; Monocytes - transplantation; Neural networks; Neurons; patients; Pilocarpine - pharmacology; Polymerase chain reaction; Rats; Rats, Wistar; Seizures; Seizures - chemically induced; Seizures - prevention & control; Spatial discrimination learning; spatial memory; Stem cells; Swimming; Temporal lobe; Temporal lobe epilepsy
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2011.06.006

Epilepsy affects 0.5–1% of the world's population, and approximately a third of these patients are refractory to current medication. Given their ability to proliferate, differentiate and regenerate tissues, stem cells could restore neural circuits lost during the course of the disease and reestablish the physiological excitability of neurons. This study verified the therapeutic potential of bone marrow mononuclear cells (BMMCs) on seizure control and cognitive impairment caused by experimentally induced epilepsy. Status epilepticus (SE) was induced by lithium–pilocarpine injection and controlled with diazepam 90min after SE onset. Lithium–pilocarpine-treated rats were intravenously transplanted 22days after SE with BMMCs obtained from enhanced green fluorescent protein (eGFP) transgenic C57BL/6 mice. Control epileptic animals were given an equivalent volume of saline or fibroblast injections. Animals were video-monitored for the presence of spontaneous recurrent seizures prior to and following the cell administration procedure. In addition, rats underwent cognitive evaluation using a Morris water maze. Our data show that BMMCs reduced the frequency of seizures and improved the learning and long-term spatial memory impairments of epileptic rats. EGFP-positive cells were detected in the brains of transplanted animals by PCR analysis. The positive behavioral effects observed in our study indicate that BMMCs could represent a promising therapeutic option in the management of chronic temporal lobe epilepsy.