The research described in this review briefly
summarizes evidence that short term
pharmacological enhancement of noradrenergic
(NA) synaptic activity, combined with symptom
relevant experience (SRE), promotes functional
recovery of some symptoms of cortical damage
in rat, cat and human beings even when
treatment is initiated from days to weeks after
injury. A summary is provided of the numerous
drugs tested in rodent cortical injury models
which have been proven useful for predicting
beneficial or harmful effects on behavioral
outcome in human stroke. The pattern of drug
effects indicates a central role for NA in
functional recovery. Additionally, studies of the
effects of direct intraventricular infusion of
monoamine neurotransmitters are reviewed and
further support the hypothesized role of NA in
recovery from some symptoms of cortical injury.
The site of NA/SRE interaction to promote
recovery from hemiplegia apparently involves
the cerebellar hemisphere contralateral to the
cortical injury. Microinfusions of NA into the
contra- but not ipsilaterai cerebellar hemisphere
dramatically enhance recovery. Furthermore,
like its systemic action, microinfusion of the α1-
NA receptor antagonist, phenoxybenzamine,
reinstates hemiplegia. A “permanent” symptom
of motor cortex injury in the cat is the complete
loss of tactile placing contralateral to the injury
which does not spontaneously recover for as
long as seven years after ablation. This posturai
reflex is temporarily restored for 8-12 hours
following amphetamine administration.
However, this permanently lost reflex can be
enduringly restored by transplanting catecholamine secreting adrenal tissue into the
wound cavity. The experiment is reviewed in
detail and involves chromaffin cell autografts
into the frontal cortex ablation wound cavity
producing a restoration of tactile placing for the
7-10 month duration of the study. This enduring
restoration of tactile placing is considered a
result of the release of catecholamines into the
CNS from the grafted chromaffin cells found, by
histochemical methods, surviving 7-10 months
after transplant. Lastly, we attribute these
delayed treatment effects to an attenuation of a
diaschisis, or remote functional depression, in
morphologically intact areas anatomically
connected to the area of injury. The widespread
reduction of glycolytic and oxidative
metabolism, produced by focal cortical injury, is
normalized by the same treatment which
alleviates symptoms and is worsened by drugs
which exacerbate deficits. These data support
the hypothesis that providing SRE during a
period of enhanced NA synaptic activity
produces an enduring functional recovery after
cortical injury by attenuating remote functional
depression. This treatment for enhancing
recovery is especially attractive since it is
effective even when begun weeks after cortical
damage.
