Calpain inhibitor attenuated optic nerve damage in acute optic neuritis in rats.

Optic neuritis (ON), which is an acute inflammatory autoimmune demyelinating disease of the central nervous system (CNS), often occurs in multiple sclerosis (MS). ON is an early diagnostic sign in most MS patients caused by damage to the optic nerve leading to visual dysfunction. Various features of both MS and ON can be studied following induction of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in Lewis rats.

Low dose estrogen prevents neuronal degeneration and microglial reactivity in an acute model of spinal cord injury: effect of dosing, route of administration, and therapy delay.

Spinal cord injury (SCI), depending on the severity of injury, leads to neurological dysfunction and paralysis. Methylprednisolone, the only currently available therapy renders limited protection in SCI. Therefore, other therapeutic agents must be tested to maximize neuroprotection and functional recovery.

Inhibition of cysteine proteases in acute and chronic spinal cord injury.

Spinal cord injury (SCI) is a serious neurological disorder that debilitates mostly young people. Unfortunately, we still do not have suitable therapeutic agents for treatment of SCI and prevention of its devastating consequences. However, we have gained a good understanding of pathological mechanisms that cause neurodegeneration leading to paralysis or even death following SCI.

Physiological low dose of estrogen-protected neurons in experimental spinal cord injury.

A protective role for estrogen against neurodegeneration and neurotrauma has received enormous attention in recent years, unraveling multiple facets and thus establishing this steroid as a multiactive neuroprotectant. The present study briefly reports our findings on the neuroprotective efficacy of physiologically relevant low doses of estrogen in experimental spinal cord injury (SCI) in rats. The current finding further corroborates our earlier results on efficacy of pharmacological/supraphysiological levels of estrogen in SCI and adds to the significance of conducting preclinical studies on estrogen efficacy in SCI.

Neuroprotective Drugs in Traumatic CNS Injury.

Despite extensive experimental research, the numbers of neuroprotective drugs that have proven efficacy following treatment of patients with traumatic CNS injuries still remain meager. It would be worthwhile to emphasize that majority of the victims are mostly in the second or third decades of their lives. A survey on the neuroprotective molecules that has been tested experimentally and subsequently tried clinically has been found somewhat beneficial.

Therapeutic potential of melatonin in traumatic central nervous system injury.

A vast literature extolling the benefits of melatonin has accumulated during the past four decades. Melatonin was previously considered of importance to seasonal reproduction and circadian rhythmicity. Currently, it appears to be a versatile anti-oxidative and anti-nitrosative agent, a molecule with immunomodulatory actions and profound oncostatic activity, and also to play a role as a potent neuroprotectant.

Time-dependent increases in protease activities for neuronal apoptosis in spinal cords of Lewis rats during development of acute experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is characterized by axonal demyelination and neurodegeneration, the latter having been inadequately explored in the MS animal model experimental autoimmune encephalomyelitis (EAE). The purpose of this study was to examine the time-dependent correlation between increased calpain and caspase activities and neurodegeneration in spinal cord tissues from Lewis rats with acute EAE. An increase in TUNEL-positive neurons and internucleosomal DNA fragmentation in EAE spinal cords suggested that neuronal death was a result of apoptosis on days 8-10 following induction of EAE.

Direct evidence for calpain involvement in apoptotic death of neurons in spinal cord injury in rats and neuroprotection with calpain inhibitor.

To demonstrate calpain involvement in neurodegeneration in rat spinal cord injury (SCI), we examined SCI segments for DNA fragmentation, neurons for calpain overexpression, neuronal death, and neuroprotection with calpain inhibitor (E-64-d). After the induction of SCI (40 g cm force) on T12, rats were treated within 15 min with vehicle (DMSO) or E-64-d. Sham animals underwent laminectomy only.

Upregulation of calpain correlates with increased neurodegeneration in acute experimental auto-immune encephalomyelitis.

Although calpain up-regulation is well established in experimental auto-immune encephalomyelitis (EAE), a link between increased calpain expression and activity and neurodegeneration has not been examined. Therefore, spinal cord tissue from Lewis rats with EAE was examined to test the hypothesis that increased calpain expression in neurons would correlate with increased cell death and axonal damage in a time-dependent manner following EAE induction. We found that increased calpain expression in EAE corresponded to increased TUNEL-positive neurons and to increased expression of dephosphorylated neurofilament protein, markers of cell death and axonal degeneration, respectively.

Calpain inhibitor prevented apoptosis and maintained transcription of proteolipid protein and myelin basic protein genes in rat spinal cord injury.

Spinal cord injury (SCI) is associated with progressive neurodegeneration and dysfunction. Multiple cellular and molecular mechanisms are involved in this pathogenesis. In particular, the activation of proteases following trauma can cause apoptosis in the spinal cord.