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Int J Clin Exp Pathol 2013;6(8):1505-1515

Original Article
Effect of intra-cisternal application of kainic acid on the spinal cord and locomotor
activity in rats

Nilesh K Mitra, Tiffanie EW Goh, Thalisha Bala Krishnan, Vishna D Nadarajah, Arun K Vasavaraj, Tomoko Soga

School of Medicine, Taylor’s University, Subang Jaya, Selangor, Malaysia; Postgraduate and Research Department, International Medical
University, Bukit Jalil, Kuala lumpur, Malaysia; School of Medicine, International Medical University, Bukit Jalil, Kuala lumpur, Malaysia; Brain
Research Institute, School of Medicine & Health Sciences, Monash University Sunway Campus, Selangor Darul Ehsan, Malaysia

Received May 18, 2013; Accepted June 27, 2013; Epub July 15, 2013; Published August 1, 2013

Abstract: 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 14th 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. (IJCEP1305027).

Keywords: Amyotrophic lateral sclerosis, kainic acid, glial fibrillary acidic protein, neurofilament protein, superoxide dismutase, spinal cord

Address correspondence to: Dr. Nilesh Kumar Mitra, School of Medicine, Taylor’s University, No.1, Jalan Taylors, 47500 Subang Jaya,
Selangor, Malaysia. Phone: +60-3-56295000; Fax: +60-3-56295001; E-mail: NileshKumar.Mitra@taylors.edu.my