Nogo-A inhibition induces recovery from neglect in rats

Abstract

Neglect is a complex human cognitive spatial disorder typically induced by damage to prefrontal or posterior parietal association cortices. Behavioral treatments for neglect rarely generalize outside of the therapeutic context or across tasks within the same therapeutic context. Recovery, when it occurs, is spontaneous over the course of weeks to months, but often it is incomplete. A number of studies have indicated that anti-Nogo-A antibodies can be used to enhance plasticity and behavioral recovery following damage to motor cortex, and spinal cord. In the present studies the anti-Nogo-A antibodies IN-1, 7B12, or 11C7 were applied intraventricularly to adult rats demonstrating severe neglect produced by unilateral medial agranular cortex lesions in rats. The three separate anti-Nogo-A antibody groups were treated immediately following the medial agranular cortex lesions. Each of the three antibodies induced dramatic significant behavioral recovery from neglect relative to controls. Severing the corpus callosum to destroy inputs from the contralesional hemisphere resulted in reinstatement of severe neglect, pointing to a possible role of interhemispheric mechanisms in behavioral recovery from neglect.

Delayed Anti-Nogo-A Therapy Improves Function After Chronic Stroke in Adult Rats

“…This treatment was also effective in improving functional outcome when applied in a lesion-induced neglect model in the rat. 15 Therapy targeting a Nogo-A–related receptor, NgR, also resulted in beneficial effects in rats when administered at 1 week after stroke. 16 A recent report further showed that motor rehabilitation facilitated the effect of NEP1–40, which is a NgR competitive antagonist, in functional improvement after ischemic stroke in rats.…”

Predictors and signatures of recovery from neglect in acute stroke

“…To our mind, however, it is important to differentiate between a moderate deficit with preserved essential functional nodes and greater impairment after large critical lesions with considerably restricted ipsilesional functional resources. A supportive role for contralesional functional homologues in stroke recovery was demonstrated in animal models of large stroke 63,64 and spatial neglect, 65 and in more severe motor 12,14 and aphasic 8,13,66 stroke. We do not underestimate the role of the right PPC and right prefrontal regions; improvement in right PPC function was the main feature of recovered neglect.…”

Nogo-A Expression After Focal Ischemic Stroke in the Adult Rat

“…[3][4][5][6][7][8][9] Although myelin-associated Nogo-A is thought to be the primary source of the Nogorelated limitation of neuronal outgrowth and sprouting after injury, 1,10 -12 a growing body of data demonstrates that Nogo-A is expressed by many populations of neurons throughout the adult brain and spinal cord, and is not limited to oligodendrocytes. [13][14][15][16][17][18][19][20][21] Some have postulated that neuronal Nogo-A may be involved in normal cell-functioning separate from the postinjury outgrowth-inhibitory role observed for oligodendroglial Nogo-A, 14,22 but this remains to be determined.…”