The Effect of Repetitive Transcranial Magnetic Stimulation on Cognition in Diffuse Axonal Injury in a Rat Model.

Diffuse axonal injury (DAI) following sudden acceleration and deceleration can lead to cognitive function decline. Various treatments have been proposed. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive stimulation technique, is a potential treatment for enhancing neuroplasticity in cases of brain injury. The therapeutic efficacy of rTMS on cognitive function remains unconfirmed. This study investigated the effects of rTMS and the underlying molecular biomechanisms using a rat model of DAI. Sprague-Dawley rats (n = 18) were randomly divided into two groups: one receiving rTMS after DAI and the other without brain stimulation. All rats were subjected to sudden acceleration and deceleration using a DAI modeling machine to induce damage. MRI was performed to confirm the DAI lesion. The experimental group received rTMS at a frequency of 1 Hz over the frontal cortex for 10 min daily for five days. To assess spatial memory, we conducted the Morris water maze (MWM) test one day post-brain damage and one day after the five-day intervention. A video tracking system recorded the escape latency. After post-MWM tests, all rats were euthanized, and their brain tissues, particularly from the hippocampus, were collected for immunohistochemistry and western blot analyses. The escape latency showed no difference on the MWM test after DAI, but a significant difference was observed after rTMS between the two groups. Immunohistochemistry and western blot analyses indicated increased expression of BDNF, VEGF, and MAP2 in the hippocampal brain tissue of the DAI-T group. In conclusion, rTMS improved cognitive function in the DAI rat model. The increased expression of BDNF, VEGF, and MAP2 in the DAI-T group supports the potential use of rTMS in treating cognitive impairments associated with DAI.

Regulation of Genes Related to Cognition after tDCS in an Intermittent Hypoxic Brain Injury Rat Model.

Background: Hypoxic brain injury is a condition caused by restricted oxygen supply to the brain. Several studies have reported cognitive decline, particularly in spatial memory, after exposure to intermittent hypoxia (IH). However, the effect and mechanism of action of IH exposure on cognition have not been evaluated by analyzing gene expression after transcranial direct current stimulation (tDCS). Hence, the purpose of this study was to investigate the effects of tDCS on gene regulation and cognition in a rat model of IH-induced brain injury. Methods: Twenty-four 10-week-old male Sprague−Dawley rats were divided into two groups: IH exposed rats with no stimulation and IH-exposed rats that received tDCS. All rats were exposed to a hypoxic chamber containing 10% oxygen for twelve hours a day for five days. The stimulation group received tDCS at an intensity of 200 µA over the frontal bregma areas for 30 min each day for a week. As a behavior test, the escape latency on the Morris water maze (MWM) test was measured to assess spatial memory before and after stimulation. After seven days of stimulation, gene microarray analysis was conducted with a KEGG mapper tool. Results: Although there were no significant differences between the groups before and after stimulation, there was a significant effect of time and a significant time × group interaction on escape latency. In the microarray analysis, significant fold changes in 12 genes related to neurogenesis were found in the stimulation group after tDCS (p < 0.05, fold change > 2 times, the average of the normalized read count (RC) > 6 times). The highly upregulated genes in the stimulation group after tDCS were SOS, Raf, PI3K, Rac1, IRAK, and Bax. The highly downregulated genes in the stimulation group after tDCS were CHK, Crk, Rap1, p38, Ras, and NF-kB. Conclusion: In this study, we confirmed that SOS, Raf, PI3K, Rac1, IRAK, and Bax were upregulated and that CHK, Crk, Rap1, p38, Ras, and NF-kB were downregulated in a rat model of IH-induced brain injury after application of tDCS.

Brain Activity after Intermittent Hypoxic Brain Condition in Rats.

Hypoxic brain injury is accompanied by a decrease in various functions. It is also known that obstructive sleep apnea (OSA) can cause hypoxic brain injury. This study aimed to produce a model of an intermittent hypoxic brain condition in rats and determine the activity of the brain according to the duration of hypoxic exposure. Forty male Sprague-Dawley rats were divided into four groups: the control group (n = 10), the 2 h per day hypoxia exposure group (n = 10), the 4 h per day hypoxia exposure group (n = 10), and the 8 h per day hypoxia exposure group (n = 10). All rats were exposed to a hypoxic chamber containing 10% oxygen for five days. Positron emission tomography-computed tomography (PET-CT) brain images were acquired using a preclinical PET-CT scanner to evaluate the activity of brain metabolism. All the rats were subjected to normal conditions. After five days, PET-CT was performed to evaluate the recovery of brain metabolism. Western blot analysis and immunohistochemistry were performed with vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). The mean SUV was elevated in the 2 h per day and 4 h per day groups, and all brain regions showed increased metabolism except the amygdala on the left side, the auditory cortex on the right side, the frontal association cortex on the right side, the parietal association cortex on the right side, and the somatosensory cortex on the right side immediately after hypoxic exposure. However, there was no difference between 5 days rest after hypoxic exposure and control group. Western blot analysis revealed the most significant immunoreactivity for VEGF in the 2, 4, and 8 h per day groups compared with the control group and quantification of VEGF immunohistochemistry showed more expression in 2 and 4 h per day groups compared with the control group. However, there was no significant difference in immunoreactivity for BDNF among the groups. The duration of exposure to hypoxia may affect the activity of the brain due to angiogenesis after intermittent hypoxic brain conditions in rats.

Effects of exercise timing and intensity on neuroplasticity in a rat model of cerebral infarction.

Exercise therapy plays key roles in functional improvements during neurorehabilitation. However, it may be difficult for some people to properly perform exercise because mobility and endurance might be restricted by neurological deficits due to stroke. Additionally, there is little evidence detailing the biological mechanisms underlying the most effective swimming exercise protocols for neuroplasticity after stroke. Thus, the present study investigated the effects of swimming exercise on neuroplasticity in a cerebral infarction rat model according to the timing and intensity of exercise. A total of 45 male Sprague-Dawley rats (300 ±â€¯50 g, 10 weeks old) were subjected to photothrombotic cerebral infarction and randomly divided into five groups: non-exercise (group A, n = 9); early submaximal (group B, n = 9); early maximal (group C, n = 9); late submaximal (group D, n = 9); and late maximal (group E, n = 9). Swimming exercise was performed five times a week for 4 weeks, and cognition was evaluated with the Morris water maze (MWM) test. Assessments of superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels and immunohistochemical analyses of brain-derived neurotrophic factor (BDNF) were conducted in the ipsilesional hippocampus region. After 4 weeks of exercise, the escape latency was shorter and velocity was greater in group B than in groups A, C, D, and E (p = 0.046, p <  0.001, respectively). Furthermore, SOD activity was higher and MDA levels were lower in group B than in groups A, C, D, and E (p = 0.004, p = 0.019). The immunohistochemistry results revealed that the greatest BDNF immunoreactivity was in group B. Taken together, these results indicate that early submaximal swimming exercise may be the most effective protocol for the recovery of neurological deficits in a rat model of cerebral infarction.

Effect of regular swimming exercise to duration-intensity on neurocognitive function in cerebral infarction rat model.

Objective: This study investigated the effect of regular swimming exercise according to the duration-intensity on neurocognitive function in a cerebral infarction rat model. Methods: Forty male Sprague-Dawley 10-week-old rats, weighing 300 ± 50 g, were subjected to photothrombotic cerebral infarction. The remaining 36 rats were randomly divided into four groups (n = 9 per group: non-exercise (group A); swimming exercise of short duration-intensity (5 min/day, group B); swimming exercise of moderate duration-intensity (10 min/day, group C); and swimming exercise of long duration-intensity (20 min/day, group D). Exercise was performed five times a week for 4 weeks, beginning the day after cerebral infarction. Neurocognitive function was evaluated with the Morris water maze test. Immunohistochemistry and western blot analysis examined brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) at 4 weeks postinfarction. Results: At 4 weeks postinfarction, escape latency was found to be shorter in group C than in any of groups A, B, or D. Immunohistochemistry revealed the most significant immunoreactivity for BDNF and VEGF in group C. Western blot analysis demonstrated that BDNF and VEGF proteins were markedly expressed in group C. Conclusions: Regular swimming exercise of moderate duration-intensity may be the most effective exercise protocol for the recovery of neurocognitive function in cerebral infarction rat model.

In vitro cellular uptake of fibroin microspheres and its dependency on the cell cycle stage.

Cellular uptake of a protein microsphere was investigated in vitro. Fibroin microspheres with an average diameter of approximately 1 µm were prepared with Fluorescein isothiocyanate-dextran for the fluorescent core. Tomography, performed using confocal laser scanning microscopy, confirmed microsphere uptake into the cytoplasmic area of 3T3 cells. Flow cytometry showed that cellular uptake was proportional to the co-incubation time and the microsphere concentration. It also revealed that fibroin microspheres were internalised by 3T3 cells at different rates depending on the cell cycle stage. The following cell stages had higher concentrations of internalised microspheres: G(2)/M > S > G(0)/G(1), when using 0.1 mg of microspheres per 10(6) cells. The internalised microspheres per cell also increased in the same order of cell cycle stages when co-incubating cells with 1 mg of microspheres. These results provide information that can be used to develop fibroin microspheres for intracellular delivery of large cargos.

The effect of quadriceps-electrocutaneous stimulation on the T-reflex and the H-reflex of the soleus muscle.

OBJECTIVE: To investigate the effect of ipsilateral quadriceps-electrocutaneous stimulation on the T-reflex and the H-reflex of the soleus muscle, and to examine the interactions in human cutaneous sensation - the soleus motoneuron pathway. METHODS: The T-reflex and H-reflex tests were performed bilaterally on 50 able-bodied adults with a standardized technique using the soleus muscle. The reflexes were conditioned by electrocutaneous stimuli applied to the ipsilateral quadriceps using the optimal transcutaneous electrical nerve stimulation (TENS) machine (3 x perception, intensity 15-30 mA). The conditioning stimuli were followed by reflex tests by 30-50 ms (conditioning A) and 80-100 ms (conditioning B). The latency and amplitude of the T-reflex and H-reflex were measured before (control) and after conditioning stimuli (A and B) and at sham (placebo). RESULTS: There were no significant differences between the right and left sides and between the control and placebo in both T-reflex and H-reflex. There were significant differences in both latency and amplitude of the T-reflex only between control and conditioning A. There were no significant differences between control and conditioning tests in the H-reflex. CONCLUSIONS: The above results suggest that supraspinal center and cutaneous fusimotor reflexes, which increase the sensitivity of the soleus muscle spindle, mediate the observed motoneuron excitability changes.