Min-Wook Kim

Exercise increased BDNF and trkB in the contralateral hemisphere of the ischemic rat brain

Previous studies have suggested that brain-derived neurotrophic factor (BDNF) and trkB both have a role in plasticity following brain insults and exercise increases BDNF and trkB mRNA levels in the normal brain. We attempted to determine whether treadmill exercise improves motor function following experimental cerebral ischemia, and whether motor outcome is associated with BDNF and trkB expression. We subjected adult male Sprague-Dawley rats to a permanent ischemia, followed by either 12 days of treadmill exercise or non-exercise. In the exercise group, improvements in the motor behavior index were found and BDNF and trkB proteins in contralateral hemisphere were increased. This study suggests that after permanent brain ischemia, exercise improves motor performance and elevates BDNF and trkB proteins in the contralateral hemisphere.

Anatomic localization of motor points in gastrocnemius and soleus muscles

Kim MW, Kim JH, Yang YJ, Ko YJ: Anatomic localization of motor points in gastrocnemius and soleus muscles. Am J Phys Med Rehabil 2005;84:680–683. Objective: To identify the range of the terminal motor points of the triceps surae muscles in relation to bony landmarks. Design: Eight limbs of four male cadavers were anatomically dissected. The range of terminal motor points from the tibial nerve to each triceps surae muscle was identified related to the bony landmarks. Bony landmarks were medial and lateral epicondyles of the femur and medial and lateral malleoli of the tibia. The length of the lower leg was defined as the distance from the intercondylar line of the femur to the intermalleolar line of the tibia. The locations of the motor points were expressed as the percentage of the length of the lower leg. Results: The motor points of the medial gastrocnemius, lateral gastrocnemius, and soleus muscles were diffusely distributed along the muscle longitudinal bulk. The highest motor points of the medial gastrocnemius, lateral gastrocnemius, and soleus were located in 9.6% ± 3.5%, 12.0% ± 3.4%, and 20.5% ± 3.9%, respectively, of the length of the lower leg. The lowest motor points were located in 37.5% ± 5.5%, 37.9% ± 2.3%, and 46.7% ± 3.6%, respectively, of the length of the lower leg. Conclusions: The present study defined the longitudinal distribution pattern of terminal motor points in the triceps surae muscles. This concept can be helpful for further studies evaluating the effectiveness of the botulinum toxin injection method.

Atorvastatin attenuates mitochondrial toxin‐induced striatal degeneration, with decreasing iNOS/c‐Jun levels and activating ERK/Akt pathways

Mitochondrial dysfunction is a major contributor to neurodegeneration, and causes vulnerability to oxidative stress and the activations of downstream cell death pathways. 3‐Hydroxy‐3‐methyl‐glutaryl‐CoA reductase inhibitors, statins, were originally developed as cholesterol lowering agents, and have cholesterol‐independent anti‐excitotoxic and anti‐oxidative properties. We investigated whether atorvastatin can prevent the neurodegeneration induced by a mitochondrial toxin, 3‐nitropropionic acid (3NP), which inhibits succinate dehydrogenase complex II. Male Lewis rats were administered 3NP (63 mg/kg/day) using osmotic pumps for 5 days to induce striatal degeneration, and were also treated with either atorvastatin (1 or 10 mg/kg/day, orally) or vehicle (control) on five consecutive days. Atorvastatin‐treated rats showed fewer neurologic deficits than control animals as measured at day 3–5. Atorvastatin‐treated animals showed reduced striatal lesion volumes by Nissl staining, and decreased numbers of TUNEL‐positive apoptosis and Fluoro‐Jade C‐positive degenerating neurons at 5 days. Atorvastatin reduced the numbers of c‐Jun‐positive and p‐c‐Jun‐positive cells, as well as 3‐nitrotyrosin‐positive cells. In addition, atorvastatin increased p‐extracellular signal‐regulated kinase and p‐Akt levels, and attenuated the up‐regulation of inducible nitric oxide synthase by 3NP. When N(omega)‐nitro‐l‐arginine methyl ester hydrochloride was administered concomitantly with the 3NP infusion, atorvastatin failed to further reduce the striatal lesion volume and c‐Jun levels compared to the vehicle treatment. In summary, atorvastatin decreased striatal neurodegeneration induced by 3NP, with attenuating inducible nitric oxide synthase and c‐Jun levels as well as activating extracellular signal‐regulated kinase and Akt.

Electroacupuncture enhances motor recovery performance with brain-derived neurotrophic factor expression in rats with cerebral infarction

Objective Electroacupuncture (EA) is a traditional medicine in patients with post-stroke rehabilitation. Brain-derived neurotrophic factor (BDNF) is a potent growth factor involved in recovery following cerebral injury. The aim of the present study was to investigate whether EA increases BDNF levels and facilitates functional recovery. Methods Occlusion of the middle cerebral artery was performed in rats (N=12) followed by reperfusion. EA was applied at the GV20 (Baihui) acupoint. Motor and sensory functions were monitored on the Garcia scale for 2 weeks. Expressions of BDNF and receptor tyrosine kinase B (trkB) were determined by immunoblotting and immunohistochemistry. Results Improvement of Garcia scores, particularly in motor performance, were noted in the group with EA stimulation (p<0.05). With EA application, BDNF was elevated in the ischaemic hemisphere with increased numbers of BDNF(+) cells. Increased expression of trkB was also detected. Conclusion These results indicate that EA at GV20 improves motor recovery and stimulates BDNF/trkB expression in rats with cerebral ischaemia.

Granulocyte-colony stimulating factor attenuates striatal degeneration with activating survival pathways in 3-nitropropionic acid model of Huntington's disease.

Huntingtons disease (HD) has a mitochondrial dysfunction causing the vulnerability to the excitotoxicity and activations of multiple cell death pathways. Recent evidences suggest that the hematopoietic cytokine, granulocyte-colony stimulating factor (G-CSF), exerts pleiotropic neuroprotection in acute neural injury with activating various survival pathways. Thus, we investigated whether G-CSF can modulate neurodegeneration in an HD animal model induced by 3-nitropropionic acid (3NP), which inhibits mitochondrial succinate dehydrogenase complex II. Either G-CSF (50 microg/kg/day) or saline (as vehicle) was administered intraperitoneally for 5 days with 3NP (63 mg/kg/day) continuous osmotic pump infusion into male Lewis rats. We measured motor scales (0-8) daily and sacrificed rats at 5 days. We observed that G-CSF receptors were expressed in 3NP-induced degenerating striatum. Rats treated with G-CSF showed less degree of neurologic deficits. In the G-CSF-treated rats, the striatal lesion volume measured by Nissl staining, TUNEL+ apoptotic cells, Fluorojade C+ degenerating neurons, and c-Jun+ cells were all decreased. In western blotting, G-CSF activated survival pathways including p-ERK, p-eNOS, p-STAT3, and p-Akt. In summary, G-CSF was found to have neuroprotective effects and save striatal cells through activations of survival pathways in the 3NP-induced striatal degeneration model for HD.

Increased Expression of Neurotrophin 4 Following Focal Cerebral Ischemia in Adult Rat Brain with Treadmill Exercise

Neurotrophin 4 (NT-4) belongs to the family of neurotrophic factors, and it interacts with the tyrosine kinase B (trkB) receptor. NT-4 has neuroprotective effects following cerebral ischemia. Its role might be similar to brain-derived neurotrophic factor (BDNF), because both interact with trkB. Exercise also improves neural function by increasing neurotrophic factors. However, expression profiles of NT-4 in the brain during exercise are unknown. Here, we assessed the expressions of NT-4 and its receptor, trkB, following cerebral ischemia and hypothesized that exercise changes the expressions of NT-4 and trkB. Results showed that in a permanent middle cerebral artery occlusion rat model, ischemia decreased NT-4 and trkB expression. Immunohistochemistry showed their immunoreactivities around the region of the ischemic area. Treadmill exercise changed the expression of NT-4, which increased in the contralateral hemisphere in rats with ischemic injury. TrkB also showed similar patterns to its neurotophins. The change in NT-4 suggested that exercise might have primed NT4 production so that further injury causes slightly greater increases in NT4 compared with non-exercise controls.

Accuracy of the glenohumeral injection using the superior approach: a cadaveric study of injection accuracy.

Kim J-S, Yun JS, Kim JM, Ko YJ, Rhee WI, Ha NK, Kim M-W: Accuracy of the glenohumeral injection using the superior approach: a cadaveric study of injection accuracy. Objective:The glenohumeral joint can be accessed by anterior, posterior, or superior approach. Blind shoulder injections using anterior or posterior approach have been often inaccurate and infiltrated untargeted structures. The aim of this study was to investigate the success rate of injections in the glenohumeral joint using the superior approach. Design:Nineteen shoulders from 12 adult cadavers were anatomically dissected after a dye injection had been performed, with cadavers in the supine position. A clinician rated injection confidence scores. The dissectors rated injection accuracy scores and investigated untargeted structures penetrated. Results:The clinicians confidence scores were the highest in 18 of 19 shoulders. Superior glenohumeral injections were successful in 18 of 19 (94.7%) shoulders; however, in 3 of these 18 shoulders, the long heads of biceps tendons were penetrated. Conclusions:The glenohumeral joint injection using the superior approach is accurate and clinically useful, but caution for the likelihood of penetrating the long head of biceps tendon should be considered.

Effect of combination therapy with sodium ozagrel and panax ginseng on transient cerebral ischemia model in rats.

Sodium ozagrel (SO) prevents platelet aggregation and vasoconstriction in the cerebral ischemia. It plays an important role in the prevention of brain damage induced by cerebral ischemia/reperfusion. Recently, many animal studies have suggested that the Panax ginseng (PG) has neuroprotective effects in the ischemic brain. In this study, we assessed the neuroprotective effects that come from a combination therapy of SO and PG in rat models with middle cerebral artery occlusion (MCAO). Animals with MCAO were assigned randomly to one of the following four groups: (1) control (Con) group, (2) SO group (3 mg/kg, intravenously), (3) PG group (200 mg/kg, oral feeding), and (4) SO + PG group. The rats were subjected to a neurobehavior test including adhesive removal test and rotarod test at 1, 3, 7, 10, and 15 days after MCAO. The cerebral ischemic volume was quantified by Metamorph imaging software after 2-3-5-triphenyltetrazolium (TTC) staining. The neuronal cell survival and astrocytes expansion were assessed by immunohistofluorescence staining. In the adhesive removal test, the rats of PG or SO + PG group showed significantly better performance than those of the control group (Con: 88.1 ± 24.8, PG: 43.6 ± 11, SO + PG: 11.8 ± 7, P < .05). Notably, the combination therapy group (SO + PG) showed better performance than the SO group alone (SO: 56 ± 12, SO + PG: 11.8 ± 7, P < .05). In TTC staining for infarct volume, cerebral ischemic areas were also significantly reduced in the PG group and SO + PG group (Con: 219 ± 32, PG: 117 ± 8, SO + PG: 99 ± 11, P < .05). Immunohistofluorescence staining results showed that the group which received SO + PG group therapy had neuron cells in the normal range. They also had a low number of astrocytes and apoptotic cells compared with the control or SO group in the peri-infarction area. During astrocytes staining, compared to the SO + PG group, the PG group showed only minor differences in the number of NeuN-positive cells and quantitative analysis of infarct volume. In conclusion, these studies showed that in MCAO rat models, the combination therapy with SO and PG may provide better neuroprotective effects such as higher neuronal cell survival and inhibition of astrocytes expansion than monotherapy with SO alone.

The effect of exercise on trkA in the contralateral hemisphere of the ischemic rat brain

Activation of the trkA pathway has been widely accepted as a crucial factor for neuronal survival during cerebral ischemia. Findings from earlier studies have suggested that exercise changed neurotrophic factors and trk family in an ischemic rat model. In this study, we investigated the question of whether or not treadmill exercise improves motor function in an ischemic rat model, and whether or not the result is associated with trkA, responding to NGF. Adult male Sprague-Dawley rats underwent surgery for permanent ischemia, followed by either 12 days of treadmill exercise or non-exercise. We found that exercise increased the level of trkA and NGF proteins in the contralateral hemisphere and improved the motor behavior index. Our data indicate that treadmill exercise ameliorates motor performance via the elevation of trkA and NGF proteins in the contralateral hemisphere after permanent brain ischemia.

A Pilot Study for the Neuroprotective Effect of Gongjin-dan on Transient Middle Cerebral Artery Occlusion-Induced Ischemic Rat Brain

In this study, we investigated whether gongjin-dan improves functional recovery and has neuroprotective effects on reducing the infarct volume after transient middle cerebral artery occlusion (MCAo). Infarct volume was measured using TTC staining and glucose utilization by F-18 FDG PET. Functional improvement was evaluated with the Rota-rod, treadmill, Garcia score test, and adhesive removal test. At 14 days after MCAo, neuronal cell survival, astrocytes expansion, and apoptosis were assessed by immunohistofluorescence staining in the peri-infarct region. Also, the expression of neurotrophic factors and inflammatory cytokines such as VEGF, BDNF, Cox-2, TNF-α, IL-1β, and IL-1α was measured in ischemic hemisphere regions. The gongjin-dan-treated group showed both reduced infarct volume and increased glucose utilization. Behavior tests demonstrated a significant improvement compared to the control. Also in the gongjin-dan treated group, NeuN-positive cells were increased and number of astrocytes, microglia, and apoptotic cells was significantly decreased compared with the control group in the ischemic peri-infarct area. Furthermore, the expression of VEGF and BDNF was increased and level of Cox-2, TNF-α, IL-1β, and IL-1α was decreased. These results suggest that gongjin-dan may improve functional outcome through the rapid restoration of metabolism and can be considered as a potential neuroprotective agent.