Comparison of motor function recovery and brain changes in intracerebral hemorrhagic and ischemic rats with similar brain damage.

In this study, we compared the mechanisms of brain recovery in intracerebral hemorrhage and ischemia, focusing on synapses, glial cells, and dopamine expression, which are considered fundamental for neural recovery after stroke. Male Wistar rats were divided into intracerebral hemorrhage, ischemia, and sham surgery (SHAM) groups. The intracerebral hemorrhage group was injected with a collagenase solution, the ischemia group was injected with an endothelin-1 solution, and the SHAM group was injected with physiological saline. The motor function of these rats was evaluated using a rotarod test on days 7, 14, 21, and 28 post-surgery. On postoperative day 29, lesion volume was analyzed using Nissl staining. In addition, the protein expression levels of NeuN, GFAP, tyrosine hydroxylase, and PSD95 were analyzed in the striatum and motor cortex. There was no significant difference between the ischemia and intracerebral hemorrhage groups in terms of lesion volume in the striatum; however, the motor recovery of the intracerebral hemorrhage group occurred more rapidly than that of the ischemia group, and the intracerebral hemorrhage group exhibited higher GFAP protein expression in the motor cortex. The rapid motor recovery in intracerebral hemorrhage rats relative to that in ischemia rats may be associated with changes in astrocytes in brain regions remote from the injury site.

Effect of exercise from a very early stage after intracerebral hemorrhage on microglial and macrophage reactivity states in rats.

OBJECTIVE: This study investigated the effects of exercise, starting very early after intracerebral hemorrhage (ICH), on microglia and macrophages in a rat model. Collagenase solution was injected into the left striatum to induce ICH. METHODS: Rats were randomly assigned to receive placebo surgery without exercise (sham surgery), ICH without exercise (ICH), or ICH with very early exercise (ICH + VET). The ICH + VET group was subjected to treadmill running 6 h, 24 h, and days 2-6 after ICH. Motor function assessment was performed using the ladder test and rotarod test 3 h, 25 h, and 7 days after ICH. Postexercise brain tissue was collected on day 8 after surgery to investigate the lesion volume. Very early exercise temporarily worsened motor dysfunction. The protein expression levels of the macrophage and microglial markers CD80, CD163, and TMEM119 were analyzed 6 h, 24 h, and 8 days after ICH. Protein analysis of NeuN, GFAP, and PSD95 was also performed on day 8 after ICH. RESULTS: There was no significant difference in lesion volume between the ICH and ICH + VET groups on day 8 after ICH. Exercise from very early stage prevented elevated CD163 protein expression. CONCLUSION: Very early exercise may inhibit the activation of anti-inflammatory-associated macrophages/microglia.

Very Early Exercise Rehabilitation After Intracerebral Hemorrhage Promotes Inflammation in the Brain.

BACKGROUND: Very early exercise has been reported to exacerbate motor dysfunction; however, its mechanism is largely unknown. OBJECTIVE: This study examined the effect of very early exercise on motor recovery and associated brain damage following intracerebral hemorrhage (ICH) in rats. METHODS: Collagenase solution was injected into the left striatum to induce ICH. Rats were randomly assigned to receive placebo surgery without exercise (SHAM) or ICH without (ICH) or with very early exercise within 24 hours of surgery (ICH+VET). We observed sensorimotor behaviors before surgery, and after surgery preexercise and postexercise. Postexercise brain tissue was collected 27 hours after surgery to investigate the hematoma area, brain edema, and Il1b, Tgfb1, and Igf1 mRNA levels in the striatum and sensorimotor cortex using real-time reverse transcription polymerase chain reaction. NeuN, PSD95, and GFAP protein expression was analyzed by Western blotting. RESULTS: We observed significantly increased skillful sensorimotor impairment in the horizontal ladder test and significantly higher Il1b mRNA levels in the striatum of the ICH+VET group compared with the ICH group. NeuN protein expression was significantly reduced in both brain regions of the ICH+VET group compared with the SHAM group. CONCLUSION: Our results suggest that very early exercise may be associated with an exacerbation of motor dysfunction because of increased neuronal death and region-specific changes in inflammatory factors. These results indicate that implementing exercise within 24 hours after ICH should be performed with caution.

Early Exercise after Intracerebral Hemorrhage Inhibits Inflammation and Promotes Neuroprotection in the Sensorimotor Cortex in Rats.

The present study examined the effect of early exercise on brain damage and recovery of motor function following intracerebral hemorrhage (ICH) in rats. Subjects were randomly assigned to no training after ICH (ICH), no training after sham surgery (SHAM), early treadmill exercise after ICH (ICH + ET), and late treadmill exercise after ICH (ICH + LT) groups. The ICH + ET and ICH + LT groups were trained for seven consecutive days starting on day 2 and day 9 after surgery, respectively. At post surgery day 16, the brain was surgically excised, and lesion volume, cortical thickness, neuronal number, dendritic length, and dendritic complexity were analyzed. Expression levels of IL-1b, TGF-b1, and IGF-1 mRNAs in ipsilateral sensorimotor cortex were measured by RT-PCR. The recovery of motor function in the ICH + ET group was the most accelerated. Cortical thickness and neuronal number were significantly higher in the ICH + ET group than the ICH and ICH + LT groups. The length and complexity of dendrites were also significantly greater in the ICH + ET group compared with the ICH and ICH + LT groups. Expression of IL-1b mRNA was significantly lower in the ICH + ET group than that in the ICH group. Collectively, these results suggest that early treadmill exercise after ICH promotes recovery of sensorimotor function by preventing neuronal death and ensuing cortical atrophy and by preserving dendritic structure compared with late treadmill exercise and no exercise. Early exercise may prevent neurodegeneration and functional loss by inhibiting neuroinflammation.

A Comparison of Motor Functional Recovery and Brain Damage between Striatal Lesions Induced by Ischemia and Hemorrhage in Rats.

BACKGROUND: The purpose of this study was to evaluate the natural recovery process and tissue injury associated with cerebral hemorrhage and cerebral infarction, which were induced to the same degree, in the striatum of rats. METHODS: Male Wistar rats were divided into intracerebral hemorrhagic (ICH) and ischemia (ISC) groups, with the ICH group injected with a collagenase solution and the ISC group injected with an endothelin-1 solution. In the SHAM group, physiological saline was injected. Motor function was evaluated by the ladder and forelimb placing tests on the first day before surgery and the first, seventh, and 14th day after surgery. On day 15 after surgery, brain tissue was harvested and frozen sections were prepared. Nissl staining was performed, and the tissue loss, ventricular, and hemispheric volumes were analyzed. RESULTS: On the first day of surgery, the ICH group had significantly decreased motor function compared with the ISC group. However, subsequent recovery of motor function was faster in the ICH group than that in the ISC group. In addition, tissue loss and hemispheric volumes were significantly higher in the ISC group than those in the ICH group, whereas the ventricular volume was significantly higher in the ICH group than that in the ISC group. CONCLUSIONS: Collectively, our findings indicate that, in ICH and ISC where the brain damage involves the same site and is approximately the same size, motor function is recovered faster in ICH than that in ISC. As such, differences in secondary degeneration are likely affected.

Upward running is more beneficial than level surface or downslope running in reverting tibia bone degeneration in ovariectomized rats.

OBJECTIVE: We investigated the effects of upslope, level surface, and downslope running on indices of tibia and femur bone recovery in ovariectomized (OVX) rats. METHODS: Rats were randomly divided into five groups: one sham-operated (SHAM) group and four OVX groups. One OVX group was a non-running control (OVX-Cont) and the others performed upslope running (OVX-Up), level surface running (OVX-Level), or downslope running (OVX-Down) on a treadmill after ovariectomy. The metaphysis region of the proximal tibia, distal femur, and proximal femur were scanned by micro-computed tomography and various geometric and microarchitectural parameters as well as bone mineral density measured using bone analysis software. RESULTS: Tibial bone geometric parameters, BV/TV and trabecular thickness, were significantly improved in OVX-Up and OVX-Level groups compared to that in OVX-Cont and OVX-Down groups, and improved to a greater degree in OVX-Up group than in OVX-Level group. CONCLUSIONS: Therefore, running slope substantially influences the beneficial effects of treadmill running on OVX-induced bone degeneration, with upward running being more effective than level surface running or downslope running, likely due to the greater bone loads associated with upslope running. The benefits of upslope treadmill running were particularly observed in the proximal tibia.

Behavioral Effect of Short- and Long-Term Exercise on Motor Functional Recovery after Intracerebral Hemorrhage in Rats.

BACKGROUND: In this study, we investigated the effects of short- and long-term exercise on motor functional recovery following intracerebral hemorrhage (ICH) in rats. METHODS: Male Wistar rats were randomly divided into 5 experimental groups: ICH without training (ICH group), ICH with long-term exercise for 14days from the second day after surgery (ICH + LT group), ICH with short-term exercise for 7days from the second day after surgery (ICH + EST group), ICH with short-term exercise for 7days from the ninth day after surgery (ICH + LST group), and sham operation without training (SHAM group). ICH was induced by collagenase injection into the left striatum. Forelimb sensorimotor function was evaluated using forelimb placing and horizontal ladder tests. RESULTS: In the behavioral test, the ICH + LT and ICH + EST groups improved significantly compared with the ICH and ICH + LT groups. The ICH + LT and ICH + EST groups recovered motor function in an almost analogous pattern. CONCLUSIONS: Our results indicated that, when exercise was started from an early phase after ICH, both short- and long-term exercises had similar benefits on motor functional recovery. However, continuous training using simple treadmill running may have limitations to motor functional recovery.

Immobilization rapidly induces thioredoxin-interacting protein gene expression together with insulin resistance in rat skeletal muscle.

Acute short duration of disuse induces the development of insulin resistance for glucose uptake in rodent skeletal muscle. Because thioredoxin-interacting protein (TXNIP) has been implicated in the downregulation of insulin signaling and glucose uptake, we examined the possibility that muscle disuse rapidly induces insulin resistance via increased TXNIP mRNA and protein expression. Male Wistar rats were subjected to unilateral 6-h hindlimb immobilization by plaster cast. At the end of this period, the soleus muscles from both immobilized and contralateral nonimmobilized hindlimbs were excised and examined. The 6-h immobilization resulted in an increase in TXNIP mRNA and protein expressions together with a decrease in insulin-stimulated 2-deoxyglucose uptake in the rat soleus muscle. Additionally, in the rats euthanized 6 h after the plaster cast removal, TXNIP protein expression and insulin-stimulated glucose uptake in the immobilized muscle had both been restored to a normal level. Various interventions (pretreatment with transcription inhibitor actinomycin D or AMP-dependent protein kinase activator 5-aminoimidazole-4-carboxamide ribonucleotide) also suppressed the increase in TXNIP protein expression in 6-h-immobilized muscle together with partial prevention of insulin resistance for glucose uptake. These results suggested the possibility that increased TXNIP protein expression in immobilized rat soleus muscles was associated with the rapid induction of insulin resistance for glucose uptake in that tissue. NEW & NOTEWORTHY The cellular mechanism by which disuse rapidly induces muscle insulin resistance for glucose uptake remains to be identified. Using a rat hindlimb immobilization model, our findings suggest the possibility that transcriptional upregulation of thioredoxin-interacting protein is associated with the immobilization-induced rapid development of insulin resistance in skeletal muscle.

Effects of Streptomycin Administration on Increases in Skeletal Muscle Fiber Permeability and Size Following Eccentric Muscle Contractions.

The purpose of this study was to investigate the preventive effect of streptomycin (Str) administration on changes in membrane permeability and the histomorphological characteristics of damaged muscle fibers following eccentric contraction (ECC ). Eighteen 7-week-old male Fischer 344 rats were randomly assigned to three groups: control (Cont), ECC, and ECC with Str (ECC + Str). The tibialis anterior (TA) muscles in both ECC groups were stimulated electrically and exhibited ECC. Evans blue dye (EBD), a marker of muscle fiber damage associated with increased membrane permeability, was injected 24 hr before TA muscle sampling. The number of EBD-positive fibers, muscle fiber cross-sectional area (CSA), and roundness were determined via histomorphological analysis. The ECC intervention resulted in an increased fraction of EBD-positive fibers, a larger CSA, and decreased roundness. The fraction of EBD-positive fibers was 79% lower in the ECC + Str group than in the ECC group. However, there was no difference in the CSA and roundness of the EBD-positive fibers between the two ECC groups. These results suggest that Str administration can reduce the number of myofibers that increase membrane permeability following ECC, but does not ameliorate the extent of fiber swelling in extant EBD-positive fibers. Anat Rec, 301:1096-1102, 2018. © 2018 Wiley Periodicals, Inc.

Motor Skills Training Enhances α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Subunit mRNA Expression in the Ipsilateral Sensorimotor Cortex and Striatum of Rats Following Intracerebral Hemorrhage.

BACKGROUND: We investigated the effects of acrobatic training (AT) on expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits in the sensorimotor cortex and striatum after intracerebral hemorrhage (ICH). METHODS: Male Wistar rats were divided into 4 groups: ICH without AT (ICH), ICH with AT (ICH + AT), sham operation without AT (SHAM), and sham operation with AT (SHAM + AT). ICH was induced by collagenase injection into the left striatum. The ICH + AT group performed 5 acrobatic tasks daily on days 4-28 post ICH. Forelimb sensorimotor function was evaluated using the forelimb placing test. On days 14 and 29, mRNA expression levels of AMPAR subunits GluR1-4 were measured by real-time reverse transcription-polymerase chain reaction. RESULTS: Forelimb placing test scores were significantly higher in the ICH + AT group than in the ICH group. Expression levels of all AMPAR subunit mRNAs were significantly higher in the ipsilateral sensorimotor cortex of rats in the ICH + AT group than in that of rats in the ICH group on day 29. GluR3 and GluR4 expression levels were reduced in the ipsilateral striatum of rats in the ICH group compared with that of rats in the SHAM group on day 14. CONCLUSIONS: These changes may play a critical role in motor skills training-induced recovery after ICH.

Motor Skills Training Improves Sensorimotor Dysfunction and Increases Microtubule-Associated Protein 2 mRNA Expression in Rats with Intracerebral Hemorrhage.

BACKGROUND: In this study, we examined the effects of motor skills training on the sensorimotor function and the expression of genes associated with synaptic plasticity after intracerebral hemorrhage (ICH) in rats. METHODS: Male Wistar rats were subjected to ICH or sham operation. ICH was caused by the injection of collagenase into the left striatum. Rats were randomly assigned to no training, acrobatic training, and sham groups. The acrobatic group performed 5 types of acrobatic tasks from 4 to 28 days after surgery. The forelimb sensorimotor function was evaluated over time using forepaw grasping, forelimb placing, and postural instability tests. At 14 and 29 days after the lesion, we analyzed the mRNA expression levels of microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor, and growth-associated protein 43 in the bilateral sensorimotor cortex (forelimb area) by real-time reverse transcription-polymerase chain reaction. RESULTS: Motor skills training in ICH rats improved the sensorimotor dysfunction significantly from the early phase. The mRNA expression level of MAP2 was upregulated in the ipsilesional sensorimotor cortex by motor skills training at 29 days after the lesion. CONCLUSIONS: Our results suggest that sensorimotor functional recovery following motor skills training after ICH is promoted by dendritic growth in the ipsilesional sensorimotor cortex.

Running exercise enhances motor functional recovery with inhibition of dendritic regression in the motor cortex after collagenase-induced intracerebral hemorrhage in rats.

Rehabilitative approaches benefit motor functional recovery after stroke and relate to neuronal plasticity. We investigated the effects of a treadmill running exercise on the motor functional recovery and neuronal plasticity after collagenase-induced striatal intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with type IV collagenase into the left striatum to induce ICH. Sham-operated animals were injected with saline instead of collagenase. The animals were randomly assigned to the sham control (SC), the sham exercise (SE), the ICH control (IC), or the ICH exercise (IE) group. The exercise groups were forced to run on a treadmill at a speed of 9 m/min for 30 min/day between days 4 and 14 after surgery. Behavioral tests were performed using a motor deficit score, a beam-walking test and a cylinder test. At fifteen days after surgery, the animals were sacrificed, and their brains were removed. The motor function of the IE group significantly improved compared with the motor function of the IC group. No significant differences in cortical thickness were found between the groups. The IC group had fewer branches and shorter dendrite lengths compared with the sham groups. However, dendritic branches and lengths were not significantly different between the IE and the other groups. Tropomyosin-related kinase B (TrkB) expression levels increased in the IE compared with IC group, but no significant differences in other protein (brain-derived neurotrophic factor, BDNF; Nogo-A; Rho-A/Rho-associated protein kinase 2, ROCK2) expression levels were found between the groups. These results suggest that improved motor function after a treadmill running exercise after ICH may be related to the prevention of dendritic regression due to TrkB upregulation.

Early constraint-induced movement therapy promotes functional recovery and neuronal plasticity in a subcortical hemorrhage model rat.

Constraint-induced movement therapy (CIMT) promotes functional recovery of impaired forelimbs after hemiplegic strokes, including intracerebral hemorrhage (ICH). We used a rat model of subcortical hemorrhage to compare the effects of delivering early or late CIMT after ICH. The rat model was made by injecting collagenase into the globus pallidus near the internal capsule, and then forcing rats to use the affected forelimb for 7 days starting either 1 day (early CIMT) or 17 days (late CIMT) after the lesion. Recovery of forelimb function in the skilled reaching test and the ladder stepping test was found after early-CIMT, while no significant recovery was shown after late CIMT or in the non-CIMT controls. Early CIMT was associated with greater numbers of ΔFosB-positive cells in the ipsi-lesional sensorimotor cortex layers II-III and V. Additionally, we found expression of the growth-related genes brain-derived neurotrophic factor (BDNF) and growth-related protein 43 (GAP-43), and abundant dendritic arborization of pyramidal neurons in the sensorimotor area. Similar results were not detected in the contra-lesional cortex. In contrast to early CIMT, late CIMT failed to induce any changes in plasticity. We conclude that CIMT induces molecular and morphological plasticity in the ipsi-lesional sensorimotor cortex and facilitates better functional recovery when initiated immediately after hemorrhage.

Motor skills training promotes motor functional recovery and induces synaptogenesis in the motor cortex and striatum after intracerebral hemorrhage in rats.

We investigated the effects of motor skills training on several types of motor function and synaptic plasticity following intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with collagenase into the left striatum to induce ICH, and they were randomly assigned to the ICH or sham groups. Each group was divided into the motor skills training (acrobatic training) and control (no exercise) groups. The acrobatic group performed acrobatic training from 4 to 28 days after surgery. Motor functions were assessed by motor deficit score, the horizontal ladder test and the wide or narrow beam walking test at several time points after ICH. The number of ΔFosB-positive cells was counted using immunohistochemistry to examine neuronal activation, and the PSD95 protein levels were analyzed by Western blotting to examine synaptic plasticity in the bilateral sensorimotor cortices and striata at 14 and 29 days after ICH. Motor skills training following ICH significantly improved gross motor function in the early phase after ICH and skilled motor coordinated function in the late phase. The number of ΔFosB-positive cells in the contralateral sensorimotor cortex in the acrobatic group significantly increased compared to the control group. PSD95 protein expression in the motor cortex significantly increased in the late phase, and in the striatum, the protein level significantly increased in the early phase by motor skills training after ICH compared to no training after ICH. We demonstrated that motor skills training improved motor function after ICH in rats and enhanced the neural activity and synaptic plasticity in the striatum and sensorimotor cortex.

Repeated short-term daily exercise ameliorates oxidative cerebral damage and the resultant motor dysfunction after transient ischemia in rats.

Long-term exercise prior to brain ischemia enhances the activities of antioxidant enzymes and leads to a significant reduction in brain damage and neurological deficits in rats subjected to transient middle cerebral artery occlusion. However, it has not been established whether relatively short-term exercise generates similar results following middle cerebral artery occlusion. We aimed to determine whether short-term exercise could reduce oxidative damage and prevent sensori-motor dysfunction. Male Wistar rats were subjected to perform daily exercise on a treadmill for 30 min at a speed of 15 m/min for 3 weeks, followed by a 90-min middle cerebral artery occlusion. Animals were assessed after middle cerebral artery occlusion for neurological deficits and sensori-motor function. Brain tissues were processed to evaluate infarct volume and oxidative damage. Oxidative stress was assessed using immunohistochemistry for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Antioxidant enzymes were evaluated using immunohistochemistry for thioredoxin and activity assay for superoxide dismutase. Exercise for 3 weeks decreased the severity of paralysis and impairment in forelimb motor coordination. Furthermore, exercise had effect on superoxide dismutase and reduced the infarct volume and the number of cells immunopositive for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Our results suggest that pre-conditioning treadmill exercise for 3 weeks is useful for ameliorating ischemia-induced brain injury.

Low-speed treadmill running exercise improves memory function after transient middle cerebral artery occlusion in rats.

Physical exercise may enhance the recovery of impaired memory function in stroke rats. However the appropriate conditions of exercise and the mechanisms underlying these beneficial effects are not yet known. Therefore, the purpose of this study was to investigate the effect exercise intensity on memory function after cerebral infarction in rats. The animals were subjected to middle cerebral artery occlusion (MCAO) for 90 min to induce stroke and were randomly assigned to four groups; Low-Ex, High-Ex, Non-Ex and Sham. On the fourth day after surgery, rats in the Low-Ex and High-Ex groups were forced to exercise using a treadmill for 30 min every day for four weeks. Memory functions were examined during the last 5 days of the experiment (27-32 days after MCAO) by three types of tests: an object recognition test, an object location test and a passive avoidance test. After the final memory test, the infarct volume, number of neurons and microtubule-associated protein 2 (MAP2) immunoreactivity in the hippocampus were analyzed by histochemistry. Memory functions in the Low-Ex group were improved in all tests. In the High-Ex group, only the passive avoidance test improved, but not the object recognition or object location tests. Both the Low-Ex and High-Ex groups had reduced infarct volumes. Although the number of neurons in the hippocampal dentate gyrus of the Low-Ex and High-Ex groups was increased, the number for the Low-Ex group increased more than that for the High-Ex group. Moreover hippocampal MAP2 immunoreactivity in the High-Ex group was reduced compared to that in the Low-Ex group. These data suggest that the effects of exercise on memory impairment after cerebral infarction depend on exercise intensity.

Early onset of forced impaired forelimb use causes recovery of forelimb skilled motor function but no effect on gross sensory-motor function after capsular hemorrhage in rats.

Intensive use of the impaired forelimb promotes behavioral recovery and induces plastic changes of the central nervous system after stroke. However, the optimal onset of intensive use treatment after stroke is controversial. In this study, we investigated whether early forced impaired limb use (FLU) initiated 24h after intracerebral hemorrhage (ICH) of the internal capsule affected behavioral recovery and histological damage. Rats were subjected to ICH via low-dose collagenase infusion or sham stroke. One day after surgery, the ipsilateral forelimbs of half of the ICH and sham rats were casted for a week to induce the use of their contralateral forelimbs. Behavioral assessments were performed on days 10-12 and 26-28 after the surgery and followed by histological assessments. Improvements in skilled reaching and coordinated stepping function were found in the FLU-treated group in comparison with the untreated group after ICH. Additionally, FLU-treated ICH animals showed more normal and precise reaching and stepping movements as compared with ICH control animals. In contrast, FLU did not have a significant impact on gross sensory-motor functions such as the motor deficit score, contact placing response and spontaneous usage of the impaired paw. The volume of tissue lost and the number of spared corticospinal neurons in lesioned motor cortex were not affected by early FLU after ICH. These findings demonstrate the efficacy of early focused use of an impaired limb after internal capsule hemorrhage.

Treadmill running improves motor function and alters dendritic morphology in the striatum after collagenase-induced intracerebral hemorrhage in rats.

It is well known that early rehabilitation is effective for functional recovery after intracerebral hemorrhage (ICH); however, the mechanisms have not been well described. The purpose of this study was to elucidate the effects of early rehabilitative therapy (treadmill running) on recovery of motor function and alteration of brain histology after ICH. Male Wistar rats, under deep anesthesia, were placed in a stereotaxic apparatus and injected with collagenase into the left striatum to induce ICH. Sham operated animals were treated with saline. All animals were randomly assigned to treadmill exercise (for 30 min/day, 9 m/min, between 4 and 14 days after surgery) and control and were designated to one of four groups: sham+control (SC), sham+treadmill (ST), ICH+control (IC), ICH+treadmill (IT). Motor deficit score (MDS) was assessed daily after surgery. Volume of tissue lost, dendritic morphology and PSD-95 protein level in the striatum were analyzed at 15 days after surgery. The MDS of IT was significantly improved compared with IC over time. There were no differences between IT and IC in the volume of tissue lost (IT: 63.8%, IC: 61.8%), spine density or PSD-95 protein level in the striatum. However, dendritic length was increased and arborization was more complex in the contralateral striatum of the IT than the IC group (IT: 1226 µm, IC: 937 µm). These data suggest that treadmill running improves motor function after ICH and that improvement may be related to alteration of dendritic morphology in the striatum.