Early Training May Exacerbate Brain Damage after Focal Brain Ischemia in the Rat

Abstract

Summary: Early overuse of a lesioned forelimb, induced by immediate immobilization of the intact forelimb after a cortical lesion, has been reported to increase tissue damage and delay functional recovery. To investigate if early training without immobilization of the intact forelimb could increase tissue loss and reduce recovery, the middle cerebral artery was ligated distal to the striatal branches in 25 male spontaneously hyper tensive rats. Control rats were housed in standard cages, train ing rats were transferred to larger cages allowing various ac tivities and received additional special training I hour a day starting either 24 hours or 7 days after the ligation. The rats Activation and training starts early after stroke onset in most stroke centers today. Evaluations of stroke units have confirmed that early mobilization reduces second ary complications and mortality and promotes long-term functional outcome (Stroke Unit Trialists ' Collaboration, 1997a,b; lndreavik et aI. , 1997). To what extent it im proves specific motor functions is less clear. Optimal time windows for specific rehabilitation interventions af ter stroke have not been defined.That experience and training can promote adaptive plasticity in the healthy brain as well as after brain le sions has been shown in many clinical and experimental studies (Rosenzweig, 1984;Jenkins and Merzenich, 1987;Pons, 1988;Bach-y-Rita, 1990;Kaas, 1991; Pas cual-Leone and Torres, 1993;Schieber, 1995; Seitz et Received December 9, 1998; final revision received February 3, 1999; accepted February 3, 1999. Supported by grants from the Swedish Medical Research Council (project 14X-4968), the Bank of Sweden Tercentenary Foundation, the Swedish Heart and Lung Foundation. the Swedish Association for the Neurologically Disabled, and the Swedish Stroke Foundation.Address correspondence and reprint requests to Dr. Barbro B. Johansson, Section for Experimental Neurology, Wallenberg Neurosci ence Center, University Hospital, S-22 1 85 Lund, Sweden.Abbreviations used: MCA, middle cerebral artery; NMDA, N methyl-D-aspartate. 997were tested on a rotating pole, in a leg placement test, and in a water maze and they were killed 6 weeks after the ligation.Delayed training resulted in the best overall performance; how ever, both training groups performed better than standard rats on the rotating pole. The cortical infarct volume was larger in the early training group than in the other two groups (P < .005), possibly related to increased glutamate release and peri-infarct cortical hyperexcitability.

Behavioral tests for preclinical intervention assessment

“…15,[62][63][64][65][66] Considerable progress is being made in designing useful, evidence-based outcome measures for human stroke diagnosis and research. It is not easy to match deficits in rats and people, but test selection and interpretation of the nature of the deficit is critical in both if translational research is to be successful.…”

Efficacy of Rehabilitative Experience Declines with Time after Focal Ischemic Brain Injury

“…Several previous studies noted an exacerbation of injury and worsened overall outcome after excessive use of the impaired limbs (i.e., by casting or enrichment) beginning immediately after the injury (Kozlowski et al, 1996;Risedal et al, 1999). Other studies report that despite exacerbation of ischemic injury, immediate exposure to environmental enrichment improves functional outcome (Risedal et al, 1999;Farrell et al, 2001), perhaps as a result of removing functionally abnormal neurons.…”

Optimal Timing of Rehabilitation: Overview of the Evidence in the Literature

“…In 1999, Risedal et al 4 reported the negative effect of early training after focal brain ischemia in their animal study, by demonstrating more prominent increased infarct volume and thalamic atrophy in the early training group than the standard and late rehabilitation group. The functional recovery was also seen delayed in the early training group, whereas the late rehabilitation group swam shorter distance, and found platform earlier than the early training group in the water maze test.…”

“…1 Adaptive plasticity in the lesioned side of the brain as well as the healthy side by rehabilitational training was observed in many clinical and experimental studies. 4 Horn et al 2 found earlier rehabilitation admission and higher level activities early in the rehabilitation process are associated with better stroke outcome.…”