Spatiotemporal Protein Atlas of Cell Death-Related Molecules in the Rat MCAO Stroke Model

Ischemic stroke and cerebral infarction triggered by the blockage of blood supply can cause damage to the brain via a complex series of pathological changes. Recently, diverse therapies have emerged as promising candidates for the treatment of stroke. These treatments exert therapeutic effects by acting on diverse target molecules and cells in different time windows from the acute to chronic phases. Here, using immunohistochemistry, we show pathophysiological changes in the brain microenvironment at the hyperacute (within 6 h), acute (1~3 days), subacute (7 days), and chronic (1 month) phases following ischemic injury. Ischemic injury in rats was induced by occluding the middle cerebral artery and was validated by magnetic resonance imaging. The progression of damage to the brain was evaluated by immunohistochemistry for NeuN⁺ neurons, GFAP⁺ astrocytes, and Iba1⁺ microglia, and by the emergence of the cell death-related molecules such as AIF, FAF1, and activated caspase-3. Our data regarding the spatial and temporal information on pathophysiological changes may warrant the investigation of the timing of administration of therapeutic treatments in preclinical studies with an animal model of stroke.

Effect of Upper Extremity Robot-Assisted Exercise on Spasticity in Stroke Patients

OBJECTIVE: To determine the efficacy of a stretching and strengthening exercise program using an upper extremity robot, as compared with a conventional occupational therapy program for upper extremity spasticity in stroke patients. METHODS: Subjects were randomly divided into a robot-assisted therapy (RT) group and a conventional rehabilitation therapy (CT) group. RT group patients received RT and CT once daily for 30 minutes each, 5 days a week, for 2 weeks. RT was performed using an upper-extremity robot (Neuro-X; Apsun Inc., Seoul, Korea), and CT was administered by occupational therapists. CT group patients received CT alone twice daily for 30 minutes, 5 days a week, for 2 weeks. Modified Ashworth Scale (MAS) was used to measure the spasticity of upper extremity. Manual muscle tests (MMT), Manual Function Tests (MFT), Brunnstrom stage, and the Korean version of Modified Barthel Index (K-MBI) were used to measure the strength and function of upper extremity. All measurements were obtained before and after 2-week treatment. RESULTS: The RT and CT groups included 22 subjects each. After treatment, both groups showed significantly lower MAS scores and significant improvement in the MMT, MFT, Brunnstrom stage, and K-MBI scores. Treatment effects showed no significant differences between the two groups. CONCLUSION: RT showed similar treatment benefits on spasticity, as compared to CT. The study results suggested that RT could be a useful method for continuous, repeatable, and relatively accurate range of motion exercise in stroke patients with spasticity.

Mesenchymal stem cells promote proliferation of endogenous neural stem cells and survival of newborn cells in a rat stroke model

Mesenchymal stem cells (MSCs) secrete bioactive factors that exert diverse responses in vivo. In the present study, we explored mechanism how MSCs may lead to higher functional recovery in the animal stroke model. Bone marrow-derived MSCs were transplanted into the brain parenchyma 3 days after induction of stroke by occluding middle cerebral artery for 2 h. Stoke induced proliferation of resident neural stem cells in subventricular zone. However, most of new born cells underwent cell death and had a limited impact on functional recovery after stroke. Transplantation of MSCs enhanced proliferation of endogenous neural stem cells while suppressing the cell death of newly generated cells. Thereby, newborn cells migrated toward ischemic territory and differentiated in ischemic boundaries into doublecortin+ neuroblasts at higher rates in animals with MSCs compared to control group. The present study indicates that therapeutic effects of MSCs are at least partly ascribed to dual functions of MSCs by enhancing endogenous neurogenesis and protecting newborn cells from deleterious environment. The results reinforce the prospects of clinical application using MSCs in the treatment of neurological disorders.