Axonal plasticity is associated with motor recovery following amphetamine treatment combined with rehabilitation after brain injury in the adult rat

• Published in: Brain research 2006-09, Vol.1111 (1), p.176-186
• Main Authors: Ramic, Maya, Emerick, April J., Bollnow, Melanie R., O'Brien, Timothy E., Tsai, Shih-Yen, Kartje, Gwendolyn L.
• Format: Article
• Language: English
• Subjects: Amphetamine - pharmacology; Amphetamine - therapeutic use; Animals; Axons - drug effects; Axons - physiology; Axons - ultrastructure; Basilar pons; Biological and medical sciences; Biotin - analogs & derivatives; Brain Injuries - drug therapy; Brain Injuries - physiopathology; Brain Injuries - rehabilitation; Central Nervous System Stimulants - pharmacology; Central Nervous System Stimulants - therapeutic use; Dextrans; Disease Models, Animal; Efferent Pathways - drug effects; Efferent Pathways - physiology; Growth Cones - drug effects; Growth Cones - physiology; Growth Cones - ultrastructure; Male; Medical sciences; Motor Cortex - drug effects; Motor Cortex - injuries; Motor Cortex - physiopathology; Motor recovery; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; Neurite outgrowth; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neuropharmacology; Paresis - drug therapy; Paresis - physiopathology; Paresis - rehabilitation; Pharmacology. Drug treatments; Physical therapy; Physical Therapy Modalities; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Psychostimulant; Pyramidal Tracts - drug effects; Pyramidal Tracts - physiology; Rats; Rats, Long-Evans; Recovery of Function - drug effects; Recovery of Function - physiology; Sensorimotor cortex; Treatment Outcome
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.06.063

Clinical and laboratory studies have suggested that amphetamine treatment when paired with rehabilitation results in improved recovery of function after stroke or traumatic brain injury. In the present study, we investigated whether new anatomical pathways developed in association with improved motor function after brain damage and amphetamine treatment linked with rehabilitation. Following a unilateral sensorimotor cortex lesion in the adult rat, amphetamine (2 mg/kg) was administered in conjunction with physiotherapy sessions on postoperative days two and five. Physiotherapy was continued twice daily for the first 3 weeks after injury, and then once daily until week six. Performance on skilled forelimb reaching and ladder rung walking was used to assess motor improvement. Our results show that animals with sensorimotor cortical lesions receiving amphetamine treatment linked with rehabilitation had significant improvement in both tasks. Neuroanatomical tracing of efferent pathways from the opposite, non-damaged cortex resulted in the novel finding that amphetamine treatment linked with rehabilitation, significantly increased axonal growth in the deafferented basilar pontine nuclei. These results support the notion that pharmacological interventions paired with rehabilitation can enhance neuronal plasticity and thereby improve functional recovery after CNS injury.