S Li1, C H Tator. 1. Division of Neurosurgery, Toronto Western Hospital and University of Toronto, Toronto, M5T 2S8 Canada.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Philip Kitchen; Mootaz M Salman; Andrea M Halsey; Charlotte Clarke-Bland; Justin A MacDonald; Hiroaki Ishida; Hans J Vogel; Sharif Almutiri; Ann Logan; Stefan Kreida; Tamim Al-Jubair; Julie Winkel Missel; Pontus Gourdon; Susanna Törnroth-Horsefield; Matthew T Conner; Zubair Ahmed; Alex C Conner; Roslyn M Bill Journal: Cell Date: 2020-05-14 Impact factor: 41.582