Effects of MK801 on evoked potentials, spinal cord blood flow and cord edema in acute spinal cord injury in rats

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 e ects of pre-and posttreatment with MK801 on axonal function, spinal cord blood¯ow (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 ®rst 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 signi®cantly lower than in the saline group. There were no di erences 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 ®rst time it has been shown that MK801 produced a blockade of glutamate excitatory transmission in a erent pathways after SCI. Further work is required to determine whether this inhibition is reversible and related to neuroprotection and functional recovery after SCI.

Acute and chronic changes in aquaporin 4 expression after spinal cord injury

“…Spinal cord edema has been well documented in the acute phase (hours/days) after SCI (Li and Tator, 1999;Sharma et al, 2005). Our results showing significant 6% increases in the water content at the site of injury corresponded well to the percentage of water content increases (edema) recorded in brain injury or SCI (Zhao et al, 2005;Li and Tator, 1999;Sharma et al, 2005).…”

“…Our results showing significant 6% increases in the water content at the site of injury corresponded well to the percentage of water content increases (edema) recorded in brain injury or SCI (Zhao et al, 2005;Li and Tator, 1999;Sharma et al, 2005). Early edema after SCI has been attributed to the well-characterized disruption of the blood spinal cord barrier (BSCB), which is known to recover by 4 weeks after SCI (Noble and Wrathall 1989;Popovich et al, 1996;Mautes et al 2000;Whetstone et al, 2003).…”

“…6A), which corresponded to the well-established early formation of edema at the site of injury (Li and Tator, 1999;Sharma et al, 2005). This early edema did not spread to lumbar regions (Fig.…”

“…Water accumulation has been documented in the acute phase after contusion spinal cord injury (SCI; Li and Tator, 1999;Sharma et al, 2005) and has been attributed to the formation of vasogenic edema. Wagner and Stewart (1981) report that edema is directly related to the amount of initial trauma (Wagner and Stewart, 1981), while Sharma et al (2005) find that the extent of edema is closely associated with the amount of SCI-induced motor dysfunction.…”

“…Water content was determined according to the protocol described in Li and Tator (1999) Immediately after sacrificing rats, three regions of spinal cords were removed: cervical, thoracic and lumbar. Those spinal cord segments were weighed on aluminum foil, dried at 105°C for 24 h, and reweighed.…”