Hypothermia has been employed during the past 30 years as a therapeutic modality for spinal cord injury (SCI) in animal models and in humans. With our newly developed rat cervical model of contusive SCI, we investigated the therapeutic efficacy of transient systemic hypothermia (beginning 5 minutes post-injury for 4 hours, 33 degrees C) with gradual rewarming (1 degrees C per hour) for the preservation of tissue and the prevention of injury-induced functional loss. A moderate cervical displacement SCI was performed in female Fischer rats, and behavior was assessed for 8 weeks. Histologically, the application of hypothermia after SCI resulted in significant increases in normal-appearing white matter (31% increase) and gray matter (38% increase) volumes, greater preservation (four-fold) of neurons immediately rostral and caudal to the injury epicenter, and enhanced sparing of axonal connections from retrogradely traced reticulospinal neurons (127% increase) compared with normothermic controls. Functionally, a faster rate of recovery in open field locomotor ability (BBB score, weeks 1-3) and improved forelimb strength, as measured by both weight-supported hanging (43% increase) and grip strength (25% increase), were obtained after hypothermia. The current study demonstrates that mild systemic hypothermia is effective for retarding tissue damage and reducing neurological deficits following a clinically relevant contusive cervical SCI.
Rationale Ecstasy (MDMA) is used predominately by adolescents and young adults. Young MDMA users are more likely than non-users to use other drugs, including cocaine. The response to stimulant drugs can be affected by environmental factors; however, little information exists about the role that housing plays in mediating effects of MDMA in adolescence. Objectives The present experiment examined whether social and environmental factors alter effects of MDMA on activity and cocaine reward. Methods Male adolescent rats were housed on PND 23. Isolated rats were housed alone (1 rat/cage) in an impoverished environment with no toys (II) or enriched with toys (IE). Social rats were housed three/cage with (SE3) or without (SI3) toys. Starting on PND 29, 5 mg/kg MDMA or saline was injected and activity was measured for 60 min once daily for five consecutive days. On PND 36–40, cocaine CPP was conducted. Results Saline vehicle-induced activity of II rats was higher than other groups, and all groups became sensitized to the locomotor-stimulant effects of MDMA. In II rats, maximal CPP was increased after MDMA pre-exposure compared to vehicle. Environmental enrichment blocked this; however, dose–effect curves for cocaine CPP shifted to the left in both IE and SE3 rats. In rats with just social enrichment, there were no effects of MDMA on cocaine CPP. Conclusion Drug prevention and treatment strategies should take into account different environments in which adolescents live. These findings show that MDMA increases cocaine reward in male adolescents, and social enrichment diminishes, while environmental enrichment enhances this.
The mechanism of SCI induced oligodendrocyte apoptosis is poorly understood. Tumor necrosis factor alpha (TNF-α) is a pleiotropic cytokine that is involved in inflammatory mediated cell death and thought to play a pivotal role in secondary pathology after SCI, including oligodendrocyte cell death. Utilizing a contusive SCI model in rat, we characterized the spatial, temporal, and cellular profiles of tnf-α expression and production acutely post-injury. Temporally, tnf-α mRNA, as assessed by RT-PCR, increased within 1 h and remained elevated through 24 h, albeit to a much lesser extent. In situ hybridization performed at 1 h revealed tnf-α mRNA throughout a cross-sectional area of the spinal cord. Though the tnf-α mRNA was diffusely distributed in the white matter, it was predominantly expressed in the gray matter. On the other hand, TNF-α protein increased by 1 h post injury and peaked at 4 h as measured by ELISA. At 1 h, 4 h, or 24 h, TNF-α immunoreactivity was present both within and adjacent to the injury epicenter; in the ventral gray matter and throughout the majority of the white matter. Using a cell specific marker (CC1) we found that oligodendrocytes were the principle TNF-α immunoreactive cell type after SCI as analyzed by stereological methods. These oligodendrocytes were also TUNEL positive, suggesting that TNF-α might be cytotoxic to oligodendrocytes acutely following cervical SCI.
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