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Results for “Neurologic Recovery”

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PubMed1993

Effects of flunarizine on neurological recovery and spinal cord blood flow in experimental spinal cord ischemia in rabbits.

BACKGROUND AND PURPOSE: The lipophilic calcium channel antagonist flunarizine has been demonstrated to be neuroprotective in several models of cerebral ischemia. Ischemic spinal cord injury may have a similar pathophysiology and hence may respond in a similar fashion. This study was designed to investigate the effects of pretreatment with flunarizine on systemic hemodynamics, spinal cord blood flow, and neurological recovery in a rabbit model of ischemic spinal cord injury. METHODS: New Zealand White rabbits were anesthetized with ketamine and xylazine and instrumented for systemic blood pressure monitoring and spinal cord blood flow measurements using the microsphere method. After pretreatment with flunarizine or vehicle, ischemic spinal cord injury was created selectively in the caudal regions of the spinal cord by cross-clamping the abdominal aorta for a period of 25 minutes. Spinal cord blood flow was measured before, during, and 15 minutes after cross-clamp removal. Animals were allowed to recover and were graded neurologically at 18 and 24 hours after ischemia. RESULTS: Flunarizine injection was associated with hypotension that was both transient and dose related. Animals pretreated with flunarizine 0.4 mg/kg had significantly improved neurological recovery scores at 18 hours after ischemia (P = .017) compared with vehicle controls. At 24 hours this effect was lessened (P = .095); however, 60% of flunarizine-treated animals retained their ability to hop, whereas all of the vehicle-treated animals were nonambulatory. CONCLUSIONS: Flunarizine has a protective effect on neurological recovery after experimental ischemic spinal cord injury. The therapeutic window is narrow, and dosing is limited by untoward hypotension. The mechanism of protection likely involves inhibition of pathological cytosolic calcium accumulation rather than a direct effect on vascular smooth muscle.

Animals↗

PubMed1984

Cerebrospinal fluid creatine kinase activity and neurologic recovery after cardiac arrest.

We evaluated prospectively the relation between cerebrospinal fluid creatine kinase activity (CSF CK) and neurologic recovery after out-of-hospital cardiac arrest. Without knowledge of the enzyme results, we determined whether patients awoke, followed commands, or had comprehensible speech. CSF CK was significantly higher in never-awakening than in awakening patients. After cardiac arrest, elevation of CSF CK predicts poor neurologic recovery.

Brain↗

PubMed1998

The influence of chronic prearrest health conditions on mortality and functional neurological recovery in cardiac arrest survivors.

PURPOSE: To study the impact of chronic prearrest health conditions on mortality and neurological recovery in patients after witnessed cardiac arrest and primary successful resuscitation. PATIENTS AND METHODS: The study was set in the community of Vienna, Austria. Data concerning cardiopulmonary resuscitation of adult patients who survived a witnessed cardiac arrest were collected according to an internationally recommended protocol (Utstein-Style). Chronic prearrest health conditions and New York Heart Association (NYHA) functional classes were evaluated. All patients were followed up for 6 months after the event or death. Adverse outcome was defined as death or severe neurological impairment. A forward stepwise logistic regression model was applied to assess the impact of pre-arrest morbidity on unfavorable outcome, expressed as odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Of 411 patients, 269 (66%) had one or more of the following pre-arrest diseases: coronary heart disease (45%), hypertension (26%), congestive heart failure (20%), diabetes mellitus (14%), chronic pulmonary disease (6%), and cerebrovascular disease (5%). In 22% a NYHA class of III or IV was present before cardiac arrest. At 6-month follow-up, 161 (40%) of the patients were alive with favorable neurological recovery; overall mortality was 57% (n = 233). Increasing NYHA classes (OR 1.4 per NYHA class increase; CI 1.1 to 1.7) and increasing age were independent predictors of adverse outcome (OR 1.03 per 10-year increase; CI 1.01 to 1.05), as were durations of cardiac arrest (OR 1.10 per 5-minute increase; CI 1.07 to 1.12) and the presence of ventricular fibrillation or tachycardia (OR 0.3; CI 0.2 to 0.5). The remaining health conditions, as listed above, were not independently associated with outcome. CONCLUSIONS: A large proportion of patients with cardiac arrest had chronic diseases before the event. The presence of impaired functional performance in patients with structural heart disease increased unfavorable outcome within 6 months in primary cardiac arrest survivors. However, the impact of chronic prearrest conditions on outcome seems to be very small, and should not influence decisions whether to withhold or withdraw therapy.

Aged↗

PubMed1989

Influence of monosialoganglioside inner ester on neurologic recovery after global cerebral ischemia in monkeys.

We assessed the consequences of transitory global cerebral ischemia and the influence of monosialoganglioside inner ester (AGF 2) treatment on neurologic outcome, cerebral blood flow, and cerebral metabolic rate in monkeys over 48 hours. Global cerebral ischemia was produced by a cervical tourniquet and a lowering of blood pressure to 6.65 kPa; recirculation followed after 30 minutes. AGF 2 (30 mg/kg) was administered intravenously immediately after initiation of recirculation and intramuscularly twice a day for 48 hours. Our results show that treatment with AGF 2 significantly accelerated the rate of neurologic recovery. Improvement was evident 5 hours after ischemia; full neurologic recovery was observed in half of the monkeys 48 hours after ischemia. This recovery was associated with a less severe reduction in cerebral blood flow without a concomitant increase in the cerebral metabolic rate.

Animals↗

PubMed1985

Neurological recovery after cardiac arrest: clinical feasibility trial of calcium blockers.

In order to determine whether the calcium blockers verapamil and/or magnesium sulfate decrease neurological morbidity after cardiac arrest, all out-of-hospital cardiac arrests (290) occurring during a nine-month period in five participating hospitals were retrospectively studied. Twenty-nine patients met the criteria for inclusion in this study. Each had an unwitnessed, out-of-hospital cardiac arrest and was comatose (no purposeful response to pain) 20 minutes after the restoration of spontaneous circulation (ROSC). Eighteen patients (calcium blocker group) received verapamil and/or magnesium sulfate at some point after ROSC, while eleven patients received standard ACLS therapy (control group). Age, arrest time, cardiopulmonary resuscitation (CPR) time, and cerebral ischemic time were comparable in the two groups. In the calcium blocker group, seven of 18 patients regained consciousness, and six of these seven survived. All six survivors appeared neurologically normal upon discharge and at three and six months of follow-up. While no demonstrably adverse effects were seen after the administration of magnesium sulfate, 56% of the patients who received verapamil had a significant drop in blood pressure. In the control group, three of 11 patients regained consciousness and two of the three left the hospital alive. Both survivors were disabled--one severely and one moderately. Follow-up after three and six months revealed no significant improvement in their disability. Overall, six of 18 patients experienced clinically complete neurological recovery in the calcium blocker group, while none of the 11 patients in the control group made a complete neurological recovery (P = 0.06).

Aged↗

PubMed1999

Effect of acrylamide on neurological recovery following spinal cord injury in rats.

Acrylamide (ACR) is a cumulative neurotoxin which causes axonal degeneration in animals and man. Industrial workers exposed to ACR have been reported to suffer from a variety of central and peripheral neuropathological symptoms including numbness of hands and feet, skin peeling and muscular weakness of legs. These reports suggest that the body burden of ACR may be a risk factor in recovery patterns following neurotrauma. The present study was designed to assess the effect of ACR on neurological recovery following spinal cord injury (SCI) in rats. Male Sprague-Dawley rats weighing 200-230 g were anaesthetised with chloral hydrate and laminectomy was performed at T 7-8 level leaving the dura intact. A compression plate (2.2 x 5.0 mm) loaded with a weight of 35 g was placed on the exposed cord for 5 minutes. Animals were divided into seven groups of eight rats each. The animals in Group 1 served as control whereas rats in Group 2 underwent laminectomy alone (sham). The rats in Group 3 to 6 were subjected to SCI as mentioned above. Animals in Groups 4, 5 and 6 also received ACR in the doses of 10 mg/kg, 20 mg/kg and 40 mg/kg, i.p., respectively in addition to SCI, whereas the rats in Group 7 received ACR alone at a dose of 40 mg/kg body weight. The first dose of ACR was given 30 minutes before SCI, followed by daily administration of drug for 7 days. Post traumatic neurological recovery was recorded daily for 10 days using a modified Tarlov score, inclined plane test and sensory and vocal score. Electrophysiological changes were assessed using somatosensory and corticomotor evoked potentials. The animals were sacrificed at different time intervals and the injured site of the spinal cord was analysed for lipid hydroperoxides (LPH), conjugated dienes (CD) and glutathione (GSH). Neuropathological changes in the spinal cord were assessed using light microscopy. The rats exposed to compression injury alone showed a maximum neurological deficit at 24 hr and then a gradual recovery was observed over a period of 10 days. The rats treated with ACR along with SCI showed poor or no recovery over a period of 10 days. Our electrophysiological and histopathological studies also confirmed that concomitant exposure to ACR produces a significant deleterious effect on the recovery from SCI. SCI induced increase in oxidative stress (increase in LPH and CD and decrease in GSH) is also exacerbated by ACR suggesting a role of free radicals. The results of this study suggest that increased body burden of ACR may retard the recovery from neurotrauma or even lead to permanent disability.

Acrylamide↗

PubMed1989

Comparison of two ester prodrugs of methylprednisolone on early neurologic recovery in a murine closed head injury model.

In prior work, methylprednisolone succinate, sodium salt (MPSS) has been shown to enhance the early neurologic recovery of moderately or severely head-injured mice. In the present study, the relative cerebroprotective potency and efficacy of MPSS was compared to another methylprednisolone ester prodrug, methylprednisolone suleptanate, sodium salt (U67590A). Male CF-1 mice received a 900 g-cm concussive head injury followed within 5 min by an intravenous bolus dose of vehicle, MPSS, or U67590A. At 1 h postinjury, the neurologic status was evaluated blindly using a grip test. Both methylprednisolone esters were found to enhance early neurologic recovery after this severe head injury. However, U67590A was four to eight times more potent than MPSS. Either a 7.5 or 15.0 mg/kg dose of U67590A produced a significant improvement in recovery while a 60.0 mg/kg dose of MPSS was required. The maximal efficacy of the two prodrugs was equal. These results indicate that the ester of methylprednisolone can greatly influence the steroid's cerebroprotective potency and that U67590A may be superior in this regard to MPSS for the acute treatment of CNS injury.

Animals↗

PubMed1992

Neurologic recovery associated with anterior decompression of spine fractures at the thoracolumbar junction (T12-L1).

Between 1981 and 1990, twenty-two patients with incomplete neurologic deficits after thoracolumbar junction fractures were treated by anterior decompression and stabilization. Two patients were unavailable for follow-up examination, eleven underwent spinal canal decompression within 48 hours of injury (Group A); and nine patients underwent surgical decompression in an average of 61 days after injury (Group B). Neurologic recovery was analyzed by a modified Frankel grading system, the ASIA motor point scale and conus medullaris function. Patients were followed for an average of 3.5 years (range, 6-92 months). No patients had any deterioration in neurologic function after surgery. Patients in Group A had a modified Frankel grade improvement with a median of two grades and a mean American Spine Injury Association motor point improvement of 21.1 +/- 4.1. Four of nine patients with conus medullaris deficits demonstrated complete functional bladder and bowel return postoperatively. Those patients in Group B had a modified Frankel grade improvement with a median of one grade and a mean ASIA motor point improvement of 7.6 +/- 1.7. None of the six patients with conus medullaris injuries showed complete improvement in bladder or bowel function postoperatively. The modified Frankel grade and ASIA motor point score improvements were significant when the two groups were compared (P less than 0.04 and P less than 0.01, respectively). In this series of patients, early anterior decompression for traumatic injuries at the thoracolumbar junction was associated with improved rates of neurologic recovery when compared to late decompression.

Adolescent↗

PubMed1996

Do changes in oxygen metabolism in the unaffected cerebral hemisphere underlie early neurological recovery after stroke? A positron emission tomography study.

BACKGROUND AND PURPOSE: Whether an initial depression of function in the unaffected hemisphere ("transcallosal diaschisis") plays a role in early neurological recovery after acute stroke remains controversial. Previous studies were confounded by lack of acute-stage assessment with follow-up and by the problem of defining a suitable control group, since preexisting stroke risk factors may influence prestroke cerebral metabolism. We evaluated with positron emission tomography (PET) the relationships between unaffected-hemisphere (ie, contralateral) oxygen consumption (cCMRO2) and quantitative neurological assessments (and their respective evolution over time) after ischemic stroke. METHODS: Among 30 consecutive patients with first-ever middle cerebral artery ischemic stroke studied with the (15)O equilibrium method, we selected all survivors (n=19; mean age, 74.6 years) who were investigated both within the first 18 hours after stroke onset (PET1; mean, 11 +/- 4 hours) and 15 to 30 days later (PET2; mean, 24 +/- 10 days), with each patient serving as his/her own control. Neurological deficits were quantified using Orgogozo's middle cerebral artery scale (N score) at each PET session. Neurological changes were calculated as changes in the N score. A late CT scan coregistered with PET provided infarct topography and volume index. RESULTS: At PET2, we observed the overall expected neurological recovery. There was a nearly significant trend for a decrease in cCMRO2 from PET1 to PET2, especially for the neocortex (P=.08, F test); in a subgroup of eight patients with large infarcts, this CMRO2 decline was significant (P<.05) in the mirror region to the infarct. There was no significant correlation (Spearman's tests) between acute-stage cCMRO2 and same-day N scores or between changes in cCMRO2 versus changes in N score from PET1 to PET2 (any region). There was a nearly significant trend for lower PET2 cCMRO2 in the subgroup of eight patients with large compared with small infarcts (P=.06). CONCLUSIONS: We found no evidence for an influence of cCMRO2 on acute-stage neurological deficit or for a role of the unaffected hemisphere in early recovery after acute MCA ischemic stroke. The decline in unaffected-hemisphere metabolism from the acute to the subacute stage in the face of overall clinical recovery appears clinically irrelevant. The fact that the neocortical cCMRO2 at PET2 tended to be lower, and declined significantly from PET1 to PET2 in the mirror region in the subgroup of patients with large infarcts, suggests that this delayed effect represents transcallosal fiber degeneration.

Aged↗

PubMed1991

The effects of a thromboxane A2 receptor antagonist on neurologic recovery after 15 min complete global brain ischemia in dogs.

The effects of a thromboxane A(2) receptor antagonist (anti-TXA(2); ONO-3708) on the neurologic recovery after 15 min complete cerebral ischemia were investigated in dogs. Complete cerebral ischemia was achieved by occlusion of the trunk of the aorta, the superior and the inferior caval vein. Seventeen dogs were divided into 2 groups; 1) control group (no drug, n = 9), 2) Anti-TXA(2) group (anti-TXA(2) 200 mcg.kg(-1) in iv bolus soon after recirculation followed by continuous infusion at a rate of 10 mcg.kg(-1).min(-1) for 3 days, n = 8). EEG, auditory brainstem response (ABR), middle latency response (MLR), and somatosensory evoked potential (SEP) recordings were obtained before ischemia, 120 min after re-circulation and on the 7th day after ischemia. The neurologic recovery score (NRS) were determined on the 3rd and the 7th day. Impaired EEG score was significantly higher in the anti-TXA(2) group on 7th day after ischemia ( P < 0.05). Anti-TXA(2) increased the reappearance rates of the ABR-Vth ( P < 0.05) and the SEP-N(3) waves ( P < 0.01) at 120 min after ischemia. The survival rate tended to be higher in the anti-TXA(2) group. However, NRS did not significantly differ in the groups.

Journal Article↗

PubMed1981

Thyrotropin-releasing hormone improves neurologic recovery after spinal trauma in cats.

Naloxone treatment improves neurologic outcome after experimentally induced spinal trauma, but this opiate-receptor antagonist may increase post-traumatic pain. In contrast, thyrotropin-releasing hormone appears to act in vivo as a partial physiologic opiate antagonist that spares analgesic systems; this activity prompted us to evaluate its effect in spinal injury. Cervical-spine trauma was produced in anesthetized cats by the Allen method. Six animals each received thyrotropin-releasing hormone, saline, or dexamethasone as an intravenous infusion over four hours, beginning one hour after injury. Neurologic recovery was significantly better after treatment with thyrotropin-releasing hormone than after saline or dexamethasone (P less than 0.01): at six weeks, the average animal given thyrotropin-releasing hormone was normal, whereas average control animals had marked spasticity. The beneficial effect of thyrotropin-releasing hormone in experimental spinal injury and its lack of effect on nociception indicate that it may have unique therapeutic potential in spinal trauma in human beings.

Animals↗

PubMed2005

Neurologic recovery and improved detrusor contractility using muscle-derived cells in rat model of unilateral pelvic nerve transection.

OBJECTIVES: To create a model of peripheral neuropathy and explore the potential of using muscle-derived cells (MDCs) to facilitate the regeneration of autonomic nerves and improve bladder function. Damage to the peripheral nerves that innervate the bladder from radical pelvic surgery is refractory to the currently available treatments. METHODS: Rat MDCs were isolated from the gastrocnemius muscle using the preplate technique. The unilateral pelvic nerve was cut in female Sprague-Dawley rats. Three experimental groups were included: control (n = 5); unilateral pelvic nerve transected with sham injection (n = 5); and unilateral pelvic nerve transected with injection of MDC (3 x 10(5) cells/site; n = 5). Two weeks after injection, the intravesical pressures were measured during electrical stimulation of the proximal transected preganglionic nerve. The contralateral major pelvic ganglion was excised to ensure that any observed bladder activity was due exclusively to inputs on the unilateral side. The rats were killed, the experimental side major pelvic ganglion was removed, and enkephalin immunoreactivity was counted. RESULTS: After unilateral pelvic nerve transection, no change occurred in bladder weight or capacity or postvoid residual urine volume. The maximal intravesical pressures for the control, sham, and MDC groups, after the contralateral pelvis had been cut, was 31.7 +/- 10.3, 9.6 +/- 4.5, and 15.2 +/- 7.7 cm H2O, respectively (P <0.05). After transecting the preganglionic pelvic nerve, the intensity of pericellular enkephalin immunoreactivity varicosities was significantly decreased in the sham group but unchanged in the MDC group compared with the control group. CONCLUSIONS: MDCs can promote peripheral autonomic nerve regeneration. The morphologic changes correlated with the functional neurologic recovery effect of MDCs. The underlying neurologic recovery mechanisms of MDCs need to be exploited.

Animals↗

PubMed1997

Blood glucose concentration after cardiopulmonary resuscitation influences functional neurological recovery in human cardiac arrest survivors.

Experimental data suggest that postischemic blood glucose concentration plays an important role in modulating both ischemic cerebral infarction and selective neuronal necrosis. This study investigated the association between functional neurological recovery and blood glucose concentrations in human cardiac arrest survivors. A group of 145 nondiabetic patients were evaluated after witnessed ventricular fibrillation cardiac arrest. Data regarding cardiac arrest were collected according to an internationally accepted protocol immediately after arrival. Blood glucose was measured on admission and 6, 12, and 24 h thereafter. To control for duration of cardiac arrest and cardiogenic shock, both known to influence outcome as well as blood glucose, levels, Spearman rank partial correlation was used. In this multivariate analysis, a high admission blood glucose level tended to be associated with poor neurological outcome (rs = -0.16, n = 142, p = 0.06). The association between high median blood glucose levels over 24 h and poor neurological outcome was strong and statistically significant (rs = -0.2, n = 145, p = 0.015). High blood glucose concentrations occurring over the first 24 h after cardiac arrest have deleterious effects on functional neurological recovery. Whether cardiac arrest survivors might benefit from reduction of blood glucose levels needs further investigation.

Adult↗

PubMed1996

Zinc supplementation is associated with improved neurologic recovery rate and visceral protein levels of patients with severe closed head injury.

Sixty-eight patients were entered into a randomized, prospective, double-blinded controlled trial of supplemental zinc versus standard zinc therapy to study the effects of zinc supplementation on neurologic recovery and nutritional/metabolic status after severe closed head injury. One month after injury, the mortality rates in the standard zinc group and the zinc-supplemented group were 26 and 12%, respectively. Glasgow Coma Scale (GCS) scores of the zinc-supplemented group exceeded the adjusted mean GCS score of the standard group at day 28 (p = 0.03). Mean motor GCS score levels of the zinc-supplemented group were significantly higher on days 15 and 21 than those of the control group (p = 0.005, p = 0.02). This trend continued on day 28 of the study (p = 0.09). The groups did not differ in serum zinc concentration, weight, energy expenditure, or total urinary nitrogen excretion after hospital admission. Mean 24-h urine zinc levels were significantly higher in the zinc-supplemented group at days 2 (p = 0.0001) and 10 (p = 0.01) after injury. Mean serum prealbumin concentrations were significantly higher in the zinc-supplemented group (p = 0.003) at 3 weeks after injury. A similar pattern was found for mean serum retinol binding protein level (p = 0.01). A significantly larger number of patients in the standard zinc group had craniotomies for evacuation of hematoma; thus a bias may have been present. The results of this study indicate that zinc supplementation during the immediate postinjury period is associated with improved rate of neurologic recovery and visceral protein concentrations for patients with severe closed head injury.

Adolescent↗

PubMedDate not supplied

Failure of flunarizine to improve cerebral blood flow or neurologic recovery in a canine model of complete cerebral ischemia.

Ten minutes of cerebral ischemia was produced in 12 dogs by temporary ligation of the venae cavae and aorta. After reperfusion the dogs received the calcium entry blocker, flunarizine, 6 micrograms/kg infused over a ten minute period. Cerebral blood flow (CBF) and metabolism (CMRO2) were measured pre-ischemia and for 2 h post-ischemia in 6 dogs. At the end of the study brain biopsies were analyzed for cerebral metabolites. Neurologic recovery was evaluated for up to 48 h post-ischemia in an additional 6 dogs. The results of each study were compared to those previously obtained in untreated animals. The cerebral blood flows (when expressed as a percent of the pre-ischemic control value) of the flunarizine-treated and untreated groups were similar throughout the post-ischemic period. Following an initial hyperemia, the CBF fell to significantly less than the pre-ischemic control values, and remained approximately 26% of control during the final 90 min in both groups. The CMRO2 was also the same for both groups. Cerebral metabolites were similar although abnormal in both groups. Flunarizine produced pulmonary edema in 5 of 6 dogs studied for neurologic recovery. Four of these dogs died within 12 h and another dog demonstrated severe neurologic damage. None of the untreated dogs developed pulmonary edema, but 6 of 7 dogs evidenced severe neurologic damage or were dead at 48 h. Thus, flunarizine failed to improve either cerebral blood flow or neurologic outcome when given after complete cerebral ischemia in the dog. A cardiodepressive effect of flunarizine might have contributed to the poor neurologic outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Nimodipine improves cerebral blood flow and neurologic recovery after complete cerebral ischemia in the dog.

Ten minutes of complete ischemia was produced in 11 dogs by temporary ligation of the aorta. Immediately before the ischemic episode, the dogs received nimodipine, a new calcium entry blocker, 10 micrograms kg-1, i.v., followed by an infusion of 1 microgram kg-1 min-1 for 2 h. Post-ischemic cerebral blood flow and metabolism were measured for 120 min in six dogs. Neurologic recovery was evaluated 48 h post-ischemia in five dogs. The results were compared to previously determined controls. Nimodipine nearly doubled cerebral blood flow in the delayed post-ischemic hypoperfusion period, compared to untreated dogs (approximately 45% versus 25% of pre-ischemic control values), but had no significant effect on metabolism. Nimodipine also improved neurologic recovery. Four of five treated dogs were normal and one was moderately damaged, whereas six of seven controls were either severely damaged or dead. This suggests that the delayed hypoperfusion state occurring after complete cerebral ischemia probably does contribute to the ultimate neurologic damage, and that nimodipine offers a potential protective effect.

Animals↗

PubMed1988

Opiate-receptor antagonist nalmefene improves neurological recovery after traumatic spinal cord injury in rats through a central mechanism.

Nalmefene is an opiate receptor antagonist, derived from naltrexone, that has a significantly longer plasma half-life than naloxone after i.v. administration and that may have enhanced activity at kappa opiate receptors. Because of the demonstrated beneficial effects of other opiate-receptor antagonists in spinal cord injury (SCI) and the postulated role of kappa opiate receptors in such injury, nalmefene treatment was evaluated in a well-characterized model of traumatic SCI in rats. In a randomized blinded study, nalmefene treatment, given as a single i.v. bolus injection at 60 min posttrauma, significantly improved neurological recovery and reduced tissue damage. Beneficial actions were dose-related. The optimal dose was 0.1 mg/kg, with diminished effects at both higher and lower doses; this is approximately 1% of the optimal naloxone dose in SCI as shown from other studies. Nalmefene, given i.t. at doses that were ineffective systemically, significantly improved neurological recovery after spinal trauma. These findings are consistent with the hypothesis that endogenous opioids, acting at opiate receptors within the spinal cord, mediate certain secondary pathophysiological changes that contribute to irreversible tissue injury. If current clinical trials with naloxone in SCI prove successful, the profile of nalmefene would make it a candidate for use in future clinical studies.

Animals↗

PubMed2000

Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats.

OBJECT: In Japan fasudil hydrochloride (HA1077), a protein kinase inhibitor, is widely administered to prevent vasospasm in patients after subarachnoid hemorrhage. The effects of fasudil on experimental spinal cord injury (SCI) were investigated and compared with those obtained using methylprednisolone. METHODS: Spinal cord contusion was induced in rats by applying an aneurysm clip extradurally to the spinal cord at T-3 for 1 minute. After injury three groups of rats were treated with intravenously administered saline (control), intraperitoneally administered fasudil (10 mg/kg), or intravenously administered methylprednisolone (four 30 mg/kg injections). Neurological recovery was evaluated periodically over 1 month by using a modified combined behavioral scale and histopathological examination. Leukocyte infiltration near the injury site was evaluated by measuring myeloperoxidase (MPO) activity at 24 hours. Spinal cord blood flow was measured at intervals up to 3 hours after injury by using laser Doppler flowmetry. In rats in the fasudil-treated group significant improvement in modified combined behavioral score was demonstrated at each time point, whereas in the methylprednisolone-treated rats no beneficial effects were shown. In the fasudil-treated group, reduction of traumatic spinal cord damage was evident histologically in the caudal portion of the injured areas, and tissue MPO activity in tissue samples was reduced. Spinal cord blood flow was not significantly different between fasudil-treated and control group rats. CONCLUSIONS: Fasudil hydrochloride showed promise of effectiveness in promoting neurological recovery after traumatic SCI. Possible mechanisms of this effect include protein kinase inhibition and decreased infiltration by neutrophils.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗