Neuroprotection by aminoguanidine after lateral fluid-percussive brain injury in rats: a combined magnetic resonance imaging, histopathologic and functional study

• Published in: Neuropharmacology Vol. 44; no. 2; pp. 253 - 263
• Main Authors: Lu, Jia, Moochhala, Shabbir, Shirhan, Md, Ng, Kian Chye, Teo, Ai Ling, Tan, Mui Hong, Moore, Xiao Lei, Wong, Meng Cheong, Ling, Eng Ang
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-02-2003; Elsevier
• Subjects: Aminoguanidine; Animals; Antigens, CD; Antigens, Neoplasm; Antigens, Surface; Avian Proteins; Basigin; Behaviour; Biological and medical sciences; Blood Proteins; Brain Injuries - drug therapy; Brain Injuries - pathology; Brain Injuries - physiopathology; Caspase 3; Caspases - metabolism; Cerebral Cortex - cytology; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Disease Models, Animal; Enzyme Inhibitors - therapeutic use; Guanidines - therapeutic use; Hand Strength - physiology; Immunohistochemistry - methods; In Situ Nick-End Labeling - methods; Lateral fluid-percussive brain injury; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Medical sciences; Membrane Glycoproteins - metabolism; Motor Activity - drug effects; Neuronal apoptosis; Neuropharmacology; Neuroprotection; Neuroprotective agent; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Pharmacology. Drug treatments; Psychomotor Performance - drug effects; Rats; Rats, Sprague-Dawley; Reflex, Acoustic - drug effects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Time Factors; Lateral fluid-percussive brain injury; Neuroprotection; Aminoguanidine; Neuronal apoptosis; Magnetic resonance imaging; Behaviour; Intraperitoneal administration; Rat; Histopathology; Investigation method; Mechanism of action; Nervous system diseases; Enzyme; Treatment efficiency; Magnetic resonance; Rodentia; Enzyme inhibitor; Functional analysis; Guanidines; Neuroprotective agent; Nitric-oxide synthase; Cerebral disorder; Vertebrata; Chemotherapy; Mammalia; Treatment; Cell death; Animal; Central nervous system disease; Oxidoreductases; Apoptosis
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(02)00380-5

The present study examined the effects of a selective inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (AG), on neuronal cell survival and post-traumatic recovery in rats following a lateral fluid percussive brain injury. Daily treatment of AG at the dosage of 100 mg/kg or normal saline was given intraperitoneally into rats starting 2 h before or 30 min after brain injury. Treatment with AG significantly reduced lesion volumes in the brains of rats after injury, as evaluated by high-resolution magnetic resonance imaging (MRI). Immunohistochemical analysis showed a marked induction of iNOS expression in brain macrophages ipsilateral to the injury. Apoptotic neurons were observed in the ipsilateral cerebral cortex by in situ terminal transferase d-UTP nick-end labelling (TUNEL) and caspase-3 immunohistochemistry. In rats receiving prophylactic or post-injury treatment of AG, the number of degenerating neurons was markedly reduced in the cerebrum compared to those receiving saline injection. The location and extent of these pathologic changes correlated with MRI findings. Neurobehavioral studies showed that rotametric performance, grip-strength score, total and ambulatory locomotor responses and acoustic startle response were reduced in rats subjected to the injury but were significantly improved in AG-treated rats. It is suggested that inhibition of iNOS by AG may represent a potential therapeutic strategy for the treatment of traumatic brain injury.