Video Illustrating Noradrenergic
Pharmacotherapy Enhancing
Recovery from Hemiplegia

rat.avi
rat.mov
 

Symptoms

The first few seconds of the video is a close up illustrating hemiplegia in the rat 24 hours after suction ablation of the right sensorimotor cortex. When on the beam the affected limbs (especially hindlimb) are not placed on the surface as in normal rats. These symptoms are best observed by placing the rat on a narrow elevated beam as few deficits are apparent when the animal is on a flat surface. Recovery from hemiplegia can be quantified by utilization of a rating scale designed for this beam-walk task (See references 1 and 2.).

This "Behavioral Assay" has proven useful for predicting drug effects on recovery after stroke in human beings (See reference 3 and 4 and 5.). In untreated rats, spontaneous recovery of locomotion occurs in about a week, whereas in the cat recovery is not complete for months. Size and location of cortical lesions effect the symptoms and recovery rate.

 

Treatment Enhanced Recovery

The remainder of the video illustrates the remarkable improvement in locomotion within 20 min. after administering a drug increasing noradrenaline (NA) release. The treated rat was given a low dose of amphetamine compared to the control rat given saline. This drug effect is mediated by NA since similar results can be produced by any drug which increases activity at a1 noradrenergic synapses including desipramine, and phenylpropanolamine which both lack stimulant effects (see reference 3 for a list of drugs tested). Enhanced recovery is also produced by indirectly increasing at a1 noradrenergic activity by blocking the negative feedback onto Locus Coruleus somata and terminals using drugs blocking a2 noradrenergic synapses. No effect is observed after administration of the b noradrenergic agonist propranolol ( See reference 2 and 3). Lastly, infusion of NA into the lateral ventricles or cerebellar cortex contralateral, but not ipsilateral, to the cortical ablation also promotes recovery. (See references 6 and 7).

 

Noradrenergic treatment effects in human stroke cases

For these effect to endure, experience relevant to the symptoms must be provided during the period of drug action (see References 1 and 3). In human stroke cases, short term acute treatment produces effects which remain significantly different one year after the stroke and ten months after cessation of treatment.

References

  1. Feeney, D. M., Gonzalez, A. and Law, W.A. Amphetamine, haloperidol and experience interact to affect rate of recovery after motor cortex injury. Science, , 217, 855-857, 1982.
  2. Sutton, R.L. and Feeney, D.M. Alpha-noradrenergic agonists and antagonists affect recovery and maintainance of beam-walking ability after sensorimotor cortex ablation in the rat. Restorative Neurology and Neuroscience, 4, 1-11, 1992.
  3. Feeney, D.M. Weisend, M.P. and Kline, A.E. Noradrenergic pharmacotherapy, intracerebral infusion and adrenal transplantation promote functional recovery after cortical damage. Journal of Neurotransplantation and Plasticity, 4, 199-214, 1994.
  4. Walker-Batson, D, Smith, P, Curtis, S, Unwin, H, Greenlee, R. Amphetamine paired with physical therapy accelerates motor recovery after stroke. Stroke 1995;26:2254-2259
  5. Goldstein L.B., SASS Study Investigators. Common drugs may influence motor recovery after stroke. Neurology;45:865-871; 1995.
  6. Boyeson, M.G. and Feeney, D.M. Intraventricular norepinephrine facilitates recovery following sensorimotor cortex injury. Pharmacology, Biochemistry and Behavior, , 35, 497-501; 1990.
  7. Boyeson M.G.and Krobert K.A. Cerebellar Norepinephrine Infusions Facilitate Recovery After Sensorimotor Cortex Injury. Brain Res Bull;29, 435-9; 1992
Animation courtesy of NHK, Dr. Katsuhiro Nishino of Akita University, Japan and The Media Technology Service of the University of New Mexico.