Nicotine Attenuates Morphological Deficits in a Contusion Model of Spinal Cord Injury

Abstract

Protection against the progression of secondary injury appears to be an effective therapeutic strategy in spinal cord injury (SCI). Evidence indicates that nicotine can induce potent neuroprotective effects against injury to spinal cord neurons. Therefore, the present study was focused on the effects of nicotine on the behavioral and morphological recovery associated with SCI. Adult male Long-Evans rats were subjected to a moderate contusion model of SCI and received subcutaneous injections of nicotine for 14 days at the dose of 0.35 or 7 mg/kg/day. The rats were examined using the BBB locomotor rating scale for 6 weeks. At the end of the BBB recording, spinal cords were examined for the volumetric tissue sparing of gray and white matters. All SCI rats demonstrated a loss of hindlimb function followed by a recovery phase that peaked at 2-3 weeks after the trauma. Compared to untreated SCI rats, chronic nicotine administration appeared to improve the recovery of the locomotor functions. Indeed, nicotine-treated animals scored consistently higher on the BBB scale indicating that the treatment altered animal behavior. However, when taking under consideration correction factors for multiple comparisons, these data did not reach significance at overall experimental levels of significance 0.05. Nevertheless, nicotine administration was effective in sparing tissue at injury epicenter and a lower dose of nicotine also resulted in significant sparing of white matter of the injured spinal cord. These results suggest that agonists of neuronal nicotinic receptors can be attractive candidates for SCI therapy.

Quantification of Locomotor Recovery following Spinal Cord Contusion in Adult Rats

“…BBB ratings of open-field locomotion improve without treatment following a mild-to-moderate contusion to the spinal cord of rats, but remain below preinjury scores (e.g., Basso et al, 1995Basso et al, , 1996Jakeman et al, 1998;Keirstead et al, 2005;Kloos et al, 2005;Popovich et al, 1999;Rabchevsky et al, 2001;Ravikumar et al, 2005). In the present experiment, BBB ratings of open-field locomotion revealed severe, initial deficits in weight-supported walking after SCI, which improved during the 6-week recovery period.…”

Impact of chronic nicotine on sciatic nerve injury in the rat

“…The effects of systemic chronic nicotine administration on overt nerve injury have not been studied extensively. Repeated administration of once daily bolus subcutaneous injection of nicotine spared spinal cord white matter and tended to improve motoric recovery following spinal cord contusion injury (Ravikumar et al, 2005). The current studies did not monitor motor functioning nor did we assess neurodegeneration at the site of peripheral nerve injury.…”

The Functional and Neuroprotective Actions of Neu2000, a Dual-Acting Pharmacological Agent, in the Treatment of Acute Spinal Cord Injury

“…Slides were randomly chosen and the gray matter was subsequently differentiated from the white matter by a modified staining protocol for Eriochrome cyanine-R (Sigma), as previously published (Rabchevsky et al, 2001;Ravikumar et al, 2005). Briefly, sections were dehydrated at room temperature in a graded ethanol series (5 min each), cleared in Hemo-De (Fisher Scientific) for 5 min, and subsequently rehydrated in a reverse graded ethanol series followed by distilled water (5 min each).…”