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
-
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.
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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.
-
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.
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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
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Goldstein L.B., SASS Study Investigators. Common drugs may influence motor
recovery after stroke. Neurology;45:865-871; 1995.
-
Boyeson, M.G. and Feeney, D.M. Intraventricular norepinephrine facilitates
recovery following sensorimotor cortex injury. Pharmacology, Biochemistry
and Behavior, , 35, 497-501; 1990.
-
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.