Effect of intra-cisternal application of kainic acid on the spinal cord and locomotor activity in rats.
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of idiopathic etiology. Glutamate excitotoxicity is one of the proposed hypotheses causing progressive death of motor neurons. We aimed to develop an experimental animal model of this disease to enhance the knowledge of pathophysiological mechanism of ALS. Male Wistar rats were infused with Kainic acid (KA) intra-cisternally for 5 days at the dosage of 50 fmol/day and 150 fmol/day. Locomotor activity, sensory function and histological changes in cervical and lumbar sections of spinal cord were evaluated. Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Protein (NFP) were used as immunohistochemical marker for reactive astrogliosis and neuronal damage respectively. Specific Superoxide Dismutase (SOD) activity of spinal cord was estimated. The locomotor activity in the parameter of observed mean action time remained reduced on 14(th) day after administration of KA. Spinal motor neurons under Nissl stain showed pyknosis of nucleus and vacuolation of neuropil. GFAP expression increased significantly in the lumbar section of the spinal cord with high dose of KA treatment (p<0.05). NFP was expressed in axonal fibres around the neurons in KA-treated rats. A significant increase in specific SOD activity in both cervical and lumbar sections of the spinal cord was found with low dose of KA treatment (p<0.05). This study concludes that spinal cord damage with some features similar to ALS can be produced by low dose intra-cisternal administration of KA.
School of Medicine, Taylor's University, Subang Jaya, Selangor, Malaysia. NileshKumar.Mitra@taylors.edu.my
Nilesh K
NK
Mitra
Tiffanie E W
TE
Goh
Thalisha
T
Bala Krishnan
Vishna D
VD
Nadarajah
Arun K
AK
Vasavaraj
Tomoko
T
Soga
D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid
Amyotrophic lateral sclerosis; glial fibrillary acidic protein; kainic acid; neurofilament protein; spinal cord; superoxide dismutase