dizocilpine-maleate and Spinal-Cord-Diseases

To determine whether MK801, an NMDA receptor antagonist, blocks glutamate excitotoxicity directly or via other mechanisms such as improving blood supply at the injury site in a rat model of spinal cord injury (SCI). In the present study, the effects of pre- and posttreatment with MK801 on axonal function, spinal cord blood flow (SCBF) and cord water content were studied after acute SCI in rats.. Somatosensory evoked potentials (SSEPs) and cerebellar evoked potentials (CEPs) were used to quantify electrophysiological function, and the hydrogen clearance technique and wet-dry weight measurements were used to measure SCBF and cord water content, respectively. Twenty rats received a 21 g clip compression injury of the cord at T1, and were then randomly and blindly allocated to either MK801 or saline groups. Each rat received an intravenous infusion of drug or saline four times during the experiment (16 min/infusion) with the first infusion (MK801 3 mg/kg) beginning 8 min pre-injury, and the other infusions (MK801 1. 5 mg/kg) at 1 h intervals after injury. Control experiments on uninjured rats were performed in 10 rats using the same procedure as above except the clip compression injury of the cord was omitted.. In the MK801 groups with or without SCI, the amplitude of the evoked potential peaks, especially the SSEPs, was significantly lower than in the saline group. There were no differences in SCBF or cord water content between the MK801 and saline groups.. Pre- and posttreatment with MK801 inhibits evoked potentials, but does not improve SCBF or cord edema after acute compression SCI in rats. For the first time it has been shown that MK801 produced a blockade of glutamate excitatory transmission in afferent pathways after SCI. Further work is required to determine whether this inhibition is reversible and related to neuroprotection and functional recovery after SCI.

Topics: Acute Disease; Animals; Body Water; Cerebellum; Dizocilpine Maleate; Edema; Evoked Potentials; Evoked Potentials, Somatosensory; Excitatory Amino Acid Antagonists; Male; Neuroprotective Agents; Random Allocation; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Spinal Cord; Spinal Cord Diseases; Synaptic Transmission

To clarify the role of N-methyl-D-aspartate (NMDA) receptors in acute spinal cord injury, changes in the intraspinal microcirculation after acute spinal cord injury in rabbits were examined. Systemic administration of MK-801, an NMDA receptor antagonist, at a dose of 5 mg/kg, significantly improved motor recovery after injury and significantly reduced edema formation at the injured site without altering spinal cord blood flow or vascular permeability at the injured site. These findings indicate that excitatory amino acids contribute to secondary spinal cord damage, especially edema formation, mediated by NMDA receptors in the early stage after injury.

Topics: Acute Disease; Animals; Blood Pressure; Capillary Permeability; Dizocilpine Maleate; Edema; Excitatory Amino Acid Antagonists; Microcirculation; Rabbits; Receptors, N-Methyl-D-Aspartate; Regional Blood Flow; Spinal Cord; Spinal Cord Diseases; Spinal Cord Injuries