Potential neuroprotective characteristics of cannabinoids on excitotoxic neurodegeneration in the spastic Han-Wistar rat

A 120 page narrative set in American, April 1865, dating from the assassination of Abraham Lincoln and through the following months. This story investigates the way human beings� cultural pasts shape people and their ideals. Lincoln�s murder and its political consequences impacted American sensibilities for decades to come. These effects are examined in the lives of these three, stylized individuals, anonymous in the sense that they are not the kinds of characters written about in history books, whose lives were significantly altered by the larger events detailed in American history. In this story, three Appalachian children, Cable Gaines, his sister Alice and a baby, Sugar, travel to the Western territories on a journey that exposes them to the changes affecting American culture in this time period. The children, social pariahs, physical and mental misfits, are escaping economic ruin and an abusive father. Poor southern farmers, the children take their history with them when they run and are chased by it, in the form of law enforcement officials and an abusive father. They experience aspects of societal change that someone reading a history focused on larger societal changes, might miss. They also reach conclusions that reflect characteristically American ideals that still shape contemporary American culture reflecting the strength of philosophical habits to which Americans remain loyal more than a hundred years later. Both exogenous and endogenous cannabinoids bind to specific CB 1 receptors found in several areas of the brain, including the cerebellum and hippocampus. Many studies on marijuana have shown that the active components of marijuana are cannabinoids that exhibit neuroprotectant properties. The current study was conducted to investigate the potential neuroprotective properties of acutely or chronically administered cannabinoids on the spastic Han-Wistar rat. Neurodegeneration in the cerebellum and hippocampus cause the spastic Han-Wistar rat to exhibit hyperactivity, fore limb tremor, and hind limbs ataxia, progressing in the loss of all motor control leading to their death at 65 days of age. A mix of 25-28 day old, same-sex, normal and mutant littermates were utilized as pairs in the study. For my acute experiments, mutant and normal siblings rats were treated with a dose of 5 mg/kg with either one of three cannabinoid agonists, anandamide, R-(+)-Win 55,212-2 (R-Win) or R-1 methanandamide or the cannabinoid antagonist SR l 41716A. Vehicle groups received 10% DMSO dissolved in 0.9% NaCl. The vehicle groups for R-1 methanandamide were given 10% ethanol in 0.9% NaCl. The injections were administered intraperitoneally (ip) twice a week for three weeks. Progressive weight gain and quantification of motor activities of the experimental rats was recorded every 3 to 5 days throughout the life span of the mutants. H&E staining was used on selected cerebellar sections used to investigate the neuroprotective effect of R-Win on the spastic rat. To enhance the prospect of eliciting a chronic response from the CBI receptor, Alzet Mini-Osmotic pumps were utilized to infuse mutant and normal siblings rats with 0.8% R-1 methanandamide or vehicle (10%) ethanol continuously at 0.25?1 per hour for 28 days. The results show that cannabinoids have limited, if any, neuroprotection in the spastic Han-Wistar mutant. Acute results showed there was no significant change in longevity when compared to the mutant controls. Mutants receiving treatment had statistically similar motor activity when compared to vehicle mutants throughout lifespan. There was a slight increase in surviving cerebellar cells and a decrease in dying cells when treated with R-Win. Chronic methanandamide treated mutants showed an 8% increase in longevity when compared to control mutants. Yet, chronic methanandamide treated mutants had a decline in weight over the control 10% ethanol mutants from day 41 onward. Further biochemical studies will be needed to understand the direct or indirect role the CB 1 receptor plays in longevity, weight and motor activity increments after chronic R-1 methanandamide administration.