Histological study on the effect of sodium azide on the corpus striatum of albino rats and the possible protective role of L-carnitine

Sodium azide is a white crystalline powder used as a broad-spectrum biocide in agriculture and as a preservative in aqueous laboratory reagents. The aim of this study was to determine the effect of sodium azide on the corpus striatum and the possible protection by L-carnitine. Twenty-four adult male albino rats, weighing 150-200 g, were used in this study. The animals were divided equally into four groups. Group I was the control group. Group II received sodium azide at a dose of 20 mg/kg/day orally for 60 consecutive days. Group III received sodium azide at the same previous dose in addition to L-carnitine at a dose of 100 mg/kg/day intraperitoneally for 60 consecutive days. Group IV received only L-carnitine at the same previous dose once daily for 60 consecutive days. At the end of the experiment, all the animals were anesthetized, the brain was dissected out and the regions of the corpus striatum were subjected to light and electron microscopic examination. Moreover, the number of degenerated nerve cells was counted and the results were analyzed statistically. By light and electron microscope, the nerve cells [pyramidal cells and granular cells] of group II animals showed degenerative changes in the form of shrunken darkly stained and hyperchromatic nuclei. Some apoptotic cells were observed. There were multinucleated giant cells in some areas and small vacuoles in the neuropil. Also, cytoplasmic vacuolations and swollen mitochondria with indistinct cristea were detected. The neuropil in some areas contained extravasation of blood elements. The nerve fibers showed fragmentation, thickening, aggregation, and defective myelination. Statistically, there was a highly significant increase in the mean number of degenerated neurons. In group III, L-carnitine preserved most of the histological and ultrastructural profile of the corpus striatum [nerve cells and nerve fibers], with a significant decrease in the rate of neuronal loss. The results of the current study showed that the administration of L-carnitine might protect against neurotoxicity produced by exposure to sodium azide

Muscarinic M1 and M3 receptor in rat striatum: A binding study

In this study, the authors set out to determine the presence of M3 muscarinic receptors in rat striatum by examining the binding of [3H]N-methyl-scopolamine([3H]NMS) to striatal membranes and its displacement by antagonists with different affinity for M1 and M3 muscarinic receptors (pirenzepine; 4-diphenylacetoxy-N-methylpiperidine methiodide, 4-DAMP; and the p-fluoro analog of hexahydro-sila-difenidol, pFHHSiD). The specific binding of [3H]NMS to membranes from rat striatum (551 ñ 40 fmol.mg prot.-1, KD 0.11 ñ 0.01 nM) was displaced in a concentration-dependent manner by all three antagonists tested. Inhibition curves best fit to a single-site model for 4-DAMP(pKi 9.1 ñ 0.1), whereas for both pirenzepine and pFHHSiD, the best fit was to the two-site model. The pKi values for the high-affinity (8.0 ñ 0.2) and low-affinity (6.7 ñ 0.2) components for pirenzepine-mediated inhibition of [3H]NMS binding correspondend to those reported for M1 and M3 receptors, respectively. The pKi values for the high-affinity (7.7 ñ 0.1) and low-affinity (7.1 ñ 0.2) components for pFHHSiD inhibition were in good agreement with those reported for M3 and M1 receptors, respectively. Altogether, these results indicate the presence in rat striatum of both M1 and M3 muscarinic receptors. These findings might be relevant to the design and use of mucarinic antagonists in the treatment of neurological disorders such as Parkinson's disease

Effect of Carbon Monoxide-Induced Hypoxia on Synaptosomal Uptake and Release of Dopamine in Rat Striatum

We studied the effect of carbon monoxide (CO)-induced hypoxia on synaptosomal uptake and release of dopamine (DA) in rat striatum. When the rats were intoxicated at a blood level of carboxyhemoglobin (HbCO), 60-70% for 3-4hrs, [3H] DA uptake was inhibited as much as 80% of control activity. This suppressed activity remained as long as 12 hrs after termination of the intoxication. After a week recovery period, the suppressed uptake activity was restored completely. When the rats were intoxicated maintaining a blood level of HbCO at 30-40% for 6-7hrs, the uptake was inhibited to 57% of the control actvity and this suppressed activity was restored within 12hrs. For the rats maintaining a blood level of HbCO at 15-25% for 6-7hrs, uptake inhibition was not shown. Acute CO intoxication(at 60-70% of HbCO for 3-4 hrs) caused an increase in K+-stimulated DA release to 147% of the control value. In conclusion, the diminished uptake and increased release of striatal DA in a CO intoxicated brain would cause an extraneuronal accumulation of DA with depletion of intraneuronal DA level, which may play a role in CO-induced hypoxic cell damage.