among the many therapeutic strategies used following neurological injuries , physical 
 exercise aids in functional recovery by increasing resistance to nerve injury , enhancing 
 neuron survival , stimulating neurogenesis , increasing learning ability , and improving 
 recognition and memory function1 . a 
 dominant theory regarding the central nervous system ( cns ) following neurological injury 
 posited that no reassortment of any type occurs in neuronal populations . since the 1990s , 
 however , various studies have identified precursor neural stem cells ( nscs ) and demonstrated 
 that neurons are generated continuously within the cns2 . it is now widely accepted that neurogenesis in adults occurs in the 
 subventricular zone of the forebrain and subgranular zone of the hippocampus3 , particularly via the proliferation , 
 differentiation , and migration of precursor nscs . these processes are regulated by 
 neurotrophic factors , such as brain - derived neurotrophic factor ( bdnf ) , nerve growth factor 
 ( ngf ) , neurotrophin-3 ( nt-3 ) , and basic fibroblast growth factor ( fgf-2 ) , which are 
 increased in the brain by physical exercise and sensory stimulation and , in turn , increase 
 the number of surviving new neurons4 , 5 . this suggests that neurological disorders , 
 such as stroke , spinal cord injury ( sci ) , and alzheimer s disease ( ad ) , are treatable6,7,8 . in animal models , forced exercise , such as treadmill running , and voluntary exercise , like 
 wheel running , are interventions that are used widely to study the effects of physical 
 exercise on the recovery of physiological function in neurological injury9 . the application of these exercises 
 following neurological injury results in increased angiogenesis in the cerebral cortex10 and enhanced neurogenesis11 and positively affects neuroplasticity , 
 recognition , and memory function12 via 
 neuroprotective actions against the structural injury of nerve cells13 and the increased expression of neurotrophic factors14 , 15 . rehabilitation therapies following neurological injury vary , based 
 on the ethological aspects of forced and voluntary exercise , including timing , period , and 
 intensity16 in terms of the recovery of 
 nerve cells . exercise intensity influences cell proliferation and neurogenesis 
 in the adult dentate gyrus , and mild exercise is more effective for cell proliferation than 
 high - intensity exercise17 . mild treadmill 
 exercise increases cell proliferation via the enhancement of insulin - like growth factor 
 ( igf)-1 and fgf-2 levels in the brain17 . moreover , lee et al.18 found that the 
 application of mild exercise in ischemic animal models resulted in a lower infarct volume 
 and greater numbers of astrocytes than high - intensity exercise , indicating that mild 
 exercise is more effective for neurological and functional recovery . astrocytes are glial 
 cells in the brain and spinal cord that are more active in proximate injury regions and act 
 in the repair and scarring process following neuronal injury19 . these glial cells contribute to functional recovery through the 
 activation of angiogenesis , neurogenesis , and the secretion of neurotrophic factors20 . accordingly , mild exercise is effective 
 for neurological recovery via the induction of astrocyte proliferation . by contrast , forced 
 exercise inhibits the degree of cell proliferation in the adult dentate gyrus , and it also 
 reduces cell proliferation by decreasing the amount of bdnf in the dentate gyrus21 . additionally , forced exercise induces 
 stress , which enhances the secretion of glucocorticoids and may initiate increased 
 corticosterone synthesis21 . otherwise , 
 long - term voluntary exercise has a considerable impact on hypothalamic - pituitary - adrenal 
 ( hpa ) axis regulation22 ; thus , 
 clarification of the association between exercise intensity and the hpa axis is needed . however , some studies have found that high - intensity exercise has more positive effects on 
 neurological recovery and neuroprotection . hayes et al.13 reported that forced exercise , with a stressful component , was 
 neuroprotective after nerve injury via upregulation of the expression of the stress - induced 
 heat shock protein ( hsp)27 and hsp70 genes . hsp27 and hsp70 have been identified in many 
 areas of the brain13 , cartilage23 , and skeletal muscle24 . in addition , these genes exhibit altered expression 
 following exposure to different environmental stresses , such as heat , exercise , infection , 
 inflammation , ischemia , and oxidative stress23,24,25 . hsp27 and hsp70 act as intracellular chaperones for other proteins with physiologically 
 neuroprotective activities25 , 26 . in particular , hsp70 regulates apoptotic cell death by 
 interfering with apoptosis - inducing factors and increasing the expression of anti - apoptotic 
 proteins via the inhibition of caspase and cytochrome c ( cyt c ) 
 release27 , 28 . the expression of the hsp27 and hsp70 genes increased 
 significantly following forced exercise , compared with voluntary exercise , and their 
 expression could play an important role in neuroprotection13 . kinni et al.29 
 investigated cerebral metabolism using the expression of glucose transporter ( glut)-1 and 
 glut-3 , phosphofructokinase ( pfk ) , lactate dehydrogenase ( ldh ) , and adenosine monophosphate 
 kinase ( ampk ) mrna and protein and found significantly greater increases following forced 
 exercise versus mild exercise . physical exercise facilitates functional recognition and memory recovery after nerve injury 
 and improves short - term and spatial memory by repressing apoptotic neuronal cell death and 
 enhancing newborn cell survival in the hippocampal dentate gyrus30 , 31 . shimada et 
 al.12 investigated the recovery of 
 memory function following different levels of exercise intensity and found that mild 
 exercise resulted in greater improvements in memory function than high - intensity exercise by 
 increasing the number of neurons in the hippocampal dentate gyrus and enhancing 
 microtubule - associated protein ( map ) expression . similarly , low - intensity exercise enhanced 
 neurogenesis and significantly increased the expression of neurotrophic factors , such as 
 bdnf , n - methyl - d - aspartate receptor type 1 ( nmdar1 ) , and vascular endothelial growth factor 
 ( vegf ) , in the dentate gyrus of the hippocampus , compared with high - intensity exercise32 . increased bdnf gene expression 
 effectively increases neurogenesis and neuroplasticity , which may have a positive effect on 
 the structural and functional recovery of neurons . by contrast , although the method of 
 exercise was different , ogonovszky et al.33 found that overtraining of swimming exercise in rat with 
 neurological disturbance improved memory and increased bdnf expression . although these studies showed some discrepancies regarding the physiological and 
 ethological effects of voluntary versus forced exercise during neurological treatment , 
 exercise intensities should be compared very carefully . they are similar , have been applied 
 in a variety of ways by different studies , and are associated with many other factors that 
 are not yet understood . determining an appropriate exercise strategy to aid recovery 
 following neurological injury also depends not only on the exercise intensity but also on 
 the timing and period .
[ purpose ] the intensity of therapeutic physical exercise is complex and sometimes 
 controversial in patients with neural injuries . 
 this review assessed whether therapeutic 
 physical exercise is beneficial according to the intensity of the physical exercise . 
 [ methods ] the authors identified clinically or scientifically relevant articles from 
 pubmed that met the inclusion criteria . [ results ] exercise training can improve body 
 strength and lead to the physiological adaptation of skeletal muscles and the nervous 
 system after neural injuries . furthermore , neurophysiological and neuropathological 
 studies show differences in the beneficial effects of forced therapeutic exercise in 
 patients with severe or mild neural injuries . forced exercise alters the distribution of 
 muscle fiber types in patients with neural injuries . based on several animal studies , 
 forced exercise may promote functional recovery following cerebral ischemia via signaling 
 molecules in ischemic brain regions . 
 [ conclusions ] this review describes several types of 
 therapeutic forced exercise and the controversy regarding the therapeutic effects in 
 experimental animals versus humans with neural injuries . 
 this review also provides a 
 therapeutic strategy for physical therapists that grades the intensity of forced exercise 
 according to the level of neural injury .