ABSTRACT
Although methylprednisolone (MP) is the standard of care in acute spinal cord injury (SCI), its functional outcome varies in clinical situation. Recent report demonstrated that MP depresses the expression of growth-promoting neurotrophic factors after acute SCI. The present study was designed to investigate whether continuous infusion of brain-derived neurotrophic factor (BDNF) after MP treatment promotes functional recovery in severe SCI. Contusion injury was produced at the T10 vertebral level of the spinal cord in adult rats. The rats received MP intravenously immediately after the injury and BDNF was infused intrathecally using an osmotic mini-pump for six weeks. Immunohistochemical methods were used to detect ED-1, Growth associated protein-43 (GAP-43), neurofilament (NF), and choline acethyl transferase (ChAT) levels. BDNF did not alter the effect of MP on hematogenous inflammatory cellular infiltration. MP treatment with BDNF infusion resulted in greater axonal survival and regeneration compared to MP treatment alone, as indicated by increases in NF and GAP-43 gene expression. Adjunctive BDNF infusion resulted in better locomotor test scores using the Basso-Beattie-Bresnahan (BBB) test. This study demonstrated that continuous infusion of BDNF after initial MP treatment improved functional recovery after severe spinal cord injury without dampening the acute effect of MP.
Subject(s)
Animals , Female , Rats , Anti-Inflammatory Agents/pharmacology , Axons/pathology , Brain-Derived Neurotrophic Factor/metabolism , Choline O-Acetyltransferase/metabolism , GAP-43 Protein/metabolism , Gene Expression Regulation , Immunohistochemistry , Methylprednisolone/metabolism , Osmosis , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Spinal Cord/pathology , Spinal Cord Injuries/pathology , Time FactorsABSTRACT
The effect of orally fed Maharishi Amrit Kalash was examined on the activities of cholinergic enzymes in the guinea pig brain. The activity of the cholinergic enzymes viz. choline-acetyltransferase and acetylcholinesterase enzymes was found to be reduced significantly (P<0.05) in the various regions of CNS of the aged guinea pigs. Oral administration of MAK(500 mg/kg body weight daily) for 2 months significantly increased (P<0.05) the activity of choline acetyltransferase and acetylcholinesterase in the older animals. The present study indicates that this food supplement can be helpful in alleviating the cholinergic deficits in the old age.
Subject(s)
Acetylcholinesterase/metabolism , Animals , Brain/drug effects , Choline O-Acetyltransferase/metabolism , Guinea Pigs , Male , Medicine, AyurvedicABSTRACT
Acetylcholine is the neurotransmitter responsible for the transmission of impulses from cholinergic neurons to cells of innervated tissues. Its biosynthesis is catalyzed by the enzyme Choline acetyltransferase that is considered to be a phenotypically specific marker for cholinergic system. It is well known that the regulation of Choline acetyltransferase activity under physiological and pathological conditions is important for development and neuronal activities of cholinergic functions. We observed the distribution of Choline acetyltransferase in sections from the normal and denervated main electric organ sections of Electrophorus electricus (L.) by immunofluorescence using a anti-Choline acetyltransferase antibody. The animals were submitted to a surgical procedure to remove about 20 nerves and after 30 and 60 days, they were sacrificed. After 30 days, the results from immunohistochemistry demonstrated an increase on the Choline acetyltransferase distribution at denervated tissue sections when compared with the sections from the normal contralateral organ. A very similar labeling was observed between normal and denervated tissue sections of the animals after 60 days. However, Choline acetyltransferase activity (nmolesACh/ min/ mg of protein) in extracts obtained from electrocyte microsomal preparation, estimated by Fonnun's method (Fonnun 1975), was 70 per cent lower in the denervated extracts.
Subject(s)
Animals , Choline O-Acetyltransferase/metabolism , Denervation , Electrophorus/metabolism , Choline O-Acetyltransferase/analysis , Microscopy, Confocal/methodsABSTRACT
QSAR studies on a series of 18 piperidine derivatives, which act as acetyl cholinesterase (AchE) inhibitors, have been performed using van der Waals volume (V omega) and topochemical index (tau). Significant correlations have been obtained, which make it clear that AchE inhibition activity is controlled dominantly by topo chemical index.
Subject(s)
Choline O-Acetyltransferase/metabolism , Cholinesterase Inhibitors/metabolism , Enzyme Activation/drug effects , Models, Biological , Piperidines/metabolism , Regression Analysis , Structure-Activity RelationshipABSTRACT
1. The activity of choline acetyltransferase (CAT) measured by a radilabeling method was significantly reduced in the heart, submandibular gland and esophagus of rats 20 days after inoculation with Trypanosoma cruzi (Y strain). 2. Normal enzyme activity was recovered in all these organs 100 days after inoculation. 3. In the transcerse colon, no change, 30% reduction and normal activity were found at days 20, 100 and 430 of infection, respectively. 4. The data indicate recovery of parasympathetic function in experimental Chagas' disease. Axonal regrowth and sprouting are discussed as possible candidates for the recovery mechanisms