• BMB Reports
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• v.55 no.10
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• pp.512-517
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• 2022

Traumatic brain injury (TBI) is brain damage which is caused by the impact of external mechanical forces. TBI can lead to the temporary or permanent impairment of physical and cognitive abilities, resulting in abnormal behavior. We recently observed that a single session of early exercise in animals with TBI improved their behavioral performance in the absence of other cognitive abnormalities. In the present study, we investigated the therapeutic effects of continuous exercise during the early stages of TBI in rats. We found that continuous low-intensity exercise in early-stage improves the locomotion recovery in the TBI of animal models; however, it does not significantly enhance short-term memory capabilities. Moreover, continuous early exercise not only reduces the protein expression of cerebral damage-related markers, such as Glial Fibrillary Acid Protein (GFAP), Neuron-Specific Enolase (NSE), S100β, Protein Gene Products 9.5 (PGP9.5), and Heat Shock Protein 70 (HSP70), but it also decreases the expression of apoptosis-related protein BAX and cleaved caspase 3. Furthermore, exercise training in animals with TBI decreases the microglia activation and the expression of inflammatory cytokines in the serum, such as CCL20, IL-13, IL-1α, and IL-1β. These findings thus demonstrate that early exercise therapy for TBI may be an effective strategy in improving physiological function, and that serum protein levels are useful biomarkers for the predicition of the effectiveness of early exercise therapy.

• Journal of Korean Critical Care Nursing
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• v.16 no.3
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• pp.99-108
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• 2023

Purpose : This retrospective study aims to provide basic data for intervention to improve clinical outcomes and identify the characteristics of the rebound hyperthermia (RHG) and non-rebound hyperthermia (NRHG) groups by checking body temperature in patients with post-cardiac arrest syndrome. Method : The study involved 118 patients who completed target temperature management (TTM) in an acute-care unit. Data were analyzed for frequency, percentages, mean, standard deviation, median, and quartiles, and compared using the chi-squared test and Mann-Whitney U-test. Results : Rebound hyperthermia (RH) was observed in 74 (62.7%) patients, predominantly male (69.5%), with an average age of 64.54 ± 15.98, and a body mass index of 23.22 ± 4.75kg/m² (overweight). Hypertension (50%) was the most common co-morbidity, followed by diabetes and heart disease (33.1%). Neuron-specific enolase levels were higher in the NRHG 24, 48, and 72 hours after recovery of spontaneous circulation (p = .037, p < .001, p = .008). The APHCHE IV was also higher in the NRHG (p < .001). RH occurred 25.49 (7.28-52.96) hours after TTM completion, lasting for 2 (1-3) hours. Temperature reduction strategies included notifying doctors, administering antipyretics, and nursing intervention, with the latter being the most common at 94.6%. Half of the subjects in the RHG and 77.3% in the NRHG fell into cerebral performance categories 3, 4, and 5 (p = .003). Conclusion : RH is more likely a body mechanism related to CPR and TTM than a result of pathogenic infection. Therefore, we require an active intervention for hyperthermia, and a patient-specific nursing intervention protocol.

• Clinical and Experimental Pediatrics
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• v.49 no.6
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• pp.677-685
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• 2006

Purpose : This study aimed to investigate whether exogenous thyroxine($T_4$) treatment to alcohol-fed dams would ameliorate the detrimental effects of alcohol on the postnatal development of neuropeptide-Y(NPY)-containing neurons of the cerebral cortex and hippocampus of the offspring. Methods : Time-pregnant rats were divided into three groups. An alcohol-fed group A received 35 calories of liquid alcohol diet daily from gestation day 6; control group B was fed a liquid diet in which dextrin replaced alcohol isocalorically; and alcohol＋$T_4$ group C received 35 calories of liquid alcohol diet and exogenous thyroxine subcutaneously. The features of the growth and maturation of rat brain tissue were observed at 0, 7, 14, 21 and 28 postnatal days via immunohistochemistry. Results : Group C showed prominent NPY immunoreactivity in the cerebral cortex compared to group A and B at P7. In group C, NPY-containing neurons were widely distributed in the all layers of cerebral cortex after P14. Also, numerical decreases of NPY-containing neuron were not found according to increasing age in group C. A decrease of NPY-containing neurons, however, was clearly observed in group A compared to group C at P28. In the hippocampus, similar patterns appeared in groups B and C after P7. Especially, in groups B and C, NPY-containing fibers formed plexus in the cerebral cortex and hippocampus at P14. Conclusion : These results suggest that the increase of NPY synthesis caused by maternal administration of exogenous thyroxine may convalesce fetal alcohol effects, one of the effects of the dysthyroid state following maternal alcohol abuse.

• Journal of Preventive Medicine and Public Health
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• v.25 no.1 s.37
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• pp.13-25
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• 1992

This study was conducted to investigate the mechanism of protective effect by sodium selenite in methylmercuric chloride neurotoxicity, increasing intracellular $Ca^{2+}$concentration of the neuron. Methylmercuric chloride of 3mg/kg of body weight was administered simultaneously with sodium selenite of 5mg/kg and pretreatment of sodium selenite via intraperitoneal injection to rats. Also, effect of methylmercuric chloride($25{\mu}M,\;50{\mu}M,\;100{\mu}M$) and sodium selenite($200{\mu}M$) on free intrasynaptosomal $Ca^{2+}$ concentration were studied using the fluorescent $Ca^{2+}$ indicator fura -2 in vitro. After the treatment, at 6, 24, and 48 hours later, mercury in the cerebral cortex, liver and kidney tissues, succlnic dehydrogenase activities, adenosin-5'-triphosphate concentration, acetylcholinesterase activities, and intracellular $Ca^{2+}$ concentration in the cerebral cortex were determined in vivo. Cerebral synaptosomes of rats were incubated with methylmercuric chloride and sodium selenite in Hepes buffer for 10 minutes and free intrasynaptosomal $Ca^{2+}$ concentration were measured with fura-2 in vitro. The results were summarized as follows ; 1. The combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ according to time significantly more increased in the cerebral cortex and decreased in the liver, kidney mercury concentrations compared to the administration of $CH_3HgCl$ only. 2. The combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ increased more succinic dehydrogenase and acetylcholinesterase activities compared to the administration of $CH_3HgCl$ only. Particularly pretreatment of $Na_2SeO_3$ significantly more compared to the administration of $CH_3HgCl$ only. The concentration of adenosine-5'-triphosphate in $Na_2SeO_3$ treatment groups revealed a favourable effect compared to the administration of $CH_3HgCl$ only. 3. Intracellular $Ca^{2+}$ concentration in administration of $CH_3HgCl$ only was increased significantly more than control group in all test hours but was increased significantly more at 48 hours only after treatment in combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ according to time interval more decreased significantly intracellular $Ca^{2+}$ concentration compared to the administration of $CH_3HgCl$ only. 4. Free intrasynaptosomal $Ca^{2+}$ concentration in the combined administration of $CH_3HgCl$ and $Na_2SeO_3$ was decreased ($24%{\sim}40%$) significantly more than the administration of $CH_3HgCl$ only. From the above results, the specific dosage of $Na_2SeO_3$ decreased increment of intracellular $Ca^{2+}$ concentration induced by administration of $CH_3HgCl$. These findings suggest the protective mechanism of $Na_2SeO_3$ on the neurotoxicity of $CH_3HgCl$.

• Journal of Life Science
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• v.17 no.2 s.82
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• pp.198-203
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• 2007

DNA transfection is a powerful tool for studying gene functions. The $Ca^{2+}$-phosphate precipitation remains one of the most popular and cost-effective transfection techniques. Mature neurons are more resistant to transfection than young ones and most other cell types, and easy to die if microenvironment changes. Here, we report a transfection protocol for mature neurons. The critical modifications are inclusion of glial cells in culture and careful control of $Ca^{2+}$-phosphate precipitation under microscope. Cerebral glial cells were grown until ${\sim}70-80%$ confluence in DMEM/10% horse serum, which was thereafter replaced with serum-free Neurobasal/Ara-C, and 319 hippocampal neurons were plated onto the glial layer Formation of fine $DNA/Ca^{2+}$-phosphate precipitates was induced using Clontech $CalPhos^{TM}$ Mammalian Transfection Kit, and the size ($0.5-1\;{\mu}m$ in diameter) and density(about 10 particles/$100\;{\mu}m^2$) were carefully controlled by the time of incubation in the medium. This modified protocol can be reliably applied for transfection of mature neurons that are maintained longer than two weeks in vitro, resulting in 10-15 healthy transfected neurons per a well of 24-well plates. The efficacy of the protocol was verified by punctate expression of $pEGFP-CaMKII{\alpha}$, a synaptic protein, and diffuse expression of pDsRed2. Our protocol provides a reliable method for transfection of mature neurons in vitro.

• Journal of Korean Neurosurgical Society
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• v.61 no.3
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• pp.363-375
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• 2018

Intraoperative monitoring (IOM) utilizes electrophysiological techniques as a surrogate test and evaluation of nervous function while a patient is under general anesthesia. They are increasingly used for procedures, both surgical and endovascular, to avoid injury during an operation, examine neurological tissue to guide the surgery, or to test electrophysiological function to allow for more complete resection or corrections. The application of IOM during pediatric brain tumor resections encompasses a unique set of technical issues. First, obtaining stable and reliable responses in children of different ages requires detailed understanding of normal age-adjusted brain-spine development. Neurophysiology, anatomy, and anthropometry of children are different from those of adults. Second, monitoring of the brain may include risk to eloquent functions and cranial nerve functions that are difficult with the usual neurophysiological techniques. Third, interpretation of signal change requires unique sets of normative values specific for children of that age. Fourth, tumor resection involves multiple considerations including defining tumor type, size, location, pathophysiology that might require maximal removal of lesion or minimal intervention. IOM techniques can be divided into monitoring and mapping. Mapping involves identification of specific neural structures to avoid or minimize injury. Monitoring is continuous acquisition of neural signals to determine the integrity of the full longitudinal path of the neural system of interest. Motor evoked potentials and somatosensory evoked potentials are representative methodologies for monitoring. Free-running electromyography is also used to monitor irritation or damage to the motor nerves in the lower motor neuron level : cranial nerves, roots, and peripheral nerves. For the surgery of infratentorial tumors, in addition to free-running electromyography of the bulbar muscles, brainstem auditory evoked potentials or corticobulbar motor evoked potentials could be combined to prevent injury of the cranial nerves or nucleus. IOM for cerebral tumors can adopt direct cortical stimulation or direct subcortical stimulation to map the corticospinal pathways in the vicinity of lesion. IOM is a diagnostic as well as interventional tool for neurosurgery. To prove clinical evidence of it is not simple. Randomized controlled prospective studies may not be possible due to ethical reasons. However, prospective longitudinal studies confirming prognostic value of IOM are available. Furthermore, oncological outcome has also been shown to be superior in some brain tumors, with IOM. New methodologies of IOM are being developed and clinically applied. This review establishes a composite view of techniques used today, noting differences between adult and pediatric monitoring.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.103-103
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• 1997

일시적인 국소 뇌허혈 rat model에서 중대뇌동맥의 폐쇄시간에 따른 뇌조직의 손상정도를 비교 조사하였다. 웅성 Wistar rats를 isoflurane 홉입마취하에서 우측 내경동맥내로 17 mm의 silicone-coated 4-0 nylon monofilament를 삽입하여, 중대뇌동맥의 기저부를 30분, 60분 또는 90분동안 폐쇄한 후 이 monofilament를 다시 밖으로 뽑아내므로써 23 시간동안 recirculation 시키는 일시적 국소 뇌허혈 rat model을 사용한 결과, 수술 후 거의 모든 rats에서 left hemiparesis 또는 좌측으로의 circling과 같은 신경학적 결손이 나타나므로써 높은 성공률을 가지고서 비교적 용이하게 뇌허혈을 유발시킬 수 있었으며, 2 mm 두께의 fresh brain coronal slices에 대하여 2,3,5-triphenyltetrazolium chloride (TTC) 염색법을 시행하여 slice surface의 사진을 찍고 computerized 영상분석법을 이용하여 필요한 면적을 측정하므로써, coronal slice의 infarction size (%)는 총 면적에 대한 infarction 면적의 %로서, 부종율 (%)은 대조측 대뇌반구 면적의 2배에 대한 동측 대뇌반구와 대조측 대뇌반구 면적 차이의 %로서 산정되어졌다. 30분 허혈군에서는 본 염색법으로는 infarction이 거의 확인되지 않았으나 60분 허혈군 (n=13)에서는 우측 somatosensory frontoparietal cortex와 striatum 양자 모두 또는 일부 rats에서는 striatum에만 국한된 ulfarction이 확인되어졌으며 90분 허혈군 (n=12)에서는 거의 대부분의 rats에서 위 두 지역 모두에서 infarction이 확인되어졌다. Infarction size (%)는 60분과 90분 허혈군 각각에서, frontal pole로부터 5 mm되는 slice에서는 11.9$\pm$1.2 (평균치$\pm$표준오차), 13.7$\pm$1.9이었으며 7 mm되는 slice에서는 19.1$\pm$1.8, 21.9$\pm$2.1이었으며 9 mm되는 slice에서는 14.7$\pm$2.4, 19.7$\pm$2.2이었다. 또한 부종율 (%)은 60분과 90분 허혈군 각각에서, frontal pole로부터 5 mm되는 slice에서는 3.1$\pm$0.6, 3.8$\pm$0.7이었으며 7 mm되는 slice에서는 3.5$\pm$0.3, 5.7$\pm$1.0이었으며 9 $\pm$되는 slice에서는 3.4$\pm$0.5, 5.7$\pm$0.9이었다. 한편 90분 동안의 중대뇌동맥 폐쇄에 따른 뇌조직 손상을 cresyl violet 염색법, NADPH-diaphorase histochemistry, GFAP immunohistochemistry를 사용하여 일부 측정한 결과, 위의 손상지역에서는 뇌신경세포체들의 shrinkage 내지는 소실됨을 확인할 수 있었으며, NADPH-diaphorase-positive neuron들도 대부분 dendrite와 axon같은 cell process들의 fragmentation, shrinkage 내지는 소실되므로써 intensity의 감소현상이 나타났으며, reactive gliosis로 말미암아 GFAP immunoreactive intensity의 증가현상이 나타났다.

• Nutrition Research and Practice
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• v.14 no.5
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• pp.438-452
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• 2020

BACKGROUND/OBJECTIVES: Brain senescence causes cognitive impairment and neurodegeneration. It has also been demonstrated that curcumin (Cur) and hesperetin (Hes), both antioxidant polyphenolic compounds, mediate anti-aging and neuroprotective effects. Therefore, the objective of this study was to investigate whether Cur, Hes, and/or their combination exert anti-aging effects in D-galactose (Dg)-induced aged neuronal cells and rats. MATERIALS/METHODS: SH-SY5Y cells differentiated in response to retinoic acid were treated with Cur (1 μM), Hes (1 μM), or a combination of both, followed by 300 mM Dg. Neuronal loss was subsequently evaluated by measuring average neurite length and analyzing expression of β-tubulin III, phosphorylated extracellular signal-regulated kinases, and neurofilament heavy polypeptide. Cellular senescence and related proteins, p16 and p21, were also investigated, including their regulation of antioxidant enzymes. In vivo, brain aging was induced by injecting 250 mg/kg body weight (b.w.) Dg. The effects of supplementing this model with 50 mg/kg b.w. Cur, 50 mg/kg b.w. Hes, or a combination of both for 3 months were subsequently evaluated. Brain aging was examined with a step-through passive avoidance test and apoptosis markers were analyzed in brain cortex tissues. RESULTS: Cur, Hes, and their combination improved neuron length and cellular senescence by decreasing the number of β-gal stained cells, down-regulated expression of p16 and p21, and up-regulated expression of antioxidant enzymes, including superoxide dismutase 1, glutathione peroxidase 1, and catalase. Administration of Cur, Hes, or their combination also tended to ameliorate cognitive impairment and suppress apoptosis in the cerebral cortex by down-regulating Bax and poly (ADP-ribose) polymerase expression and increasing Bcl-2 expression. CONCLUSIONS: Cur and Hes appear to attenuate Dg-induced brain aging via regulation of antioxidant enzymes and apoptosis. These results suggest that Cur and Hes may mediate neuroprotective effects in the aging process, and further study of these antioxidant polyphenolic compounds is warranted.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.539-546
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• 2018

Botulinum toxin type A (BoNT/A) has been used therapeutically for various conditions including dystonia, cerebral palsy, wrinkle, hyperhidrosis and pain control. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) receive orofacial nociceptive information from primary afferents and transmit the information to higher brain center. Although many studies have shown the analgesic effects of BoNT/A, the effects of BoNT/A at the central nervous system and the action mechanism are not well understood. Therefore, the effects of BoNT/A on the spontaneous postsynaptic currents (sPSCs) in the SG neurons were investigated. In whole cell voltage clamp mode, the frequency of sPSCs was increased in 18 (37.5%) neurons, decreased in 5 (10.4%) neurons and not affected in 25 (52.1%) of 48 neurons tested by BoNT/A (3 nM). Similar proportions of frequency variation of sPSCs were observed in 1 and 10 nM BoNT/A and no significant differences were observed in the relative mean frequencies of sPSCs among 1-10 nM BoNT/A. BoNT/A-induced frequency increase of sPSCs was not affected by pretreated tetrodotoxin ($0.5{\mu}M$). In addition, the frequency of sIPSCs in the presence of CNQX ($10{\mu}M$) and AP5 ($20{\mu}M$) was increased in 10 (53%) neurons, decreased in 1 (5%) neuron and not affected in 8 (42%) of 19 neurons tested by BoNT/A (3 nM). These results demonstrate that BoNT/A increases the frequency of sIPSCs on SG neurons of the Vc at least partly and can provide an evidence for rapid action of BoNT/A at the central nervous system.

• Journal of Life Science
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• v.28 no.5
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• pp.597-604
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• 2018

Although the core mechanisms of Attention Deficit/Hyperactivity Disorder (ADHD) are unknown, several ADHD-associated proteins have been studied. G-protein - coupled receptor kinase interacting protein-1 (GIT1) is a multifunctional adapter protein that affects neuron growth and dendrite formation. GIT1-deficient mice have shown ADHD-like behavior and also recovered through amphetamine treatment. In this study, gliotransmitters were investigated in both intracellular and extracellular space from GIT1-deficient mice. To measure the amount of gliotransmitters, primary astrocyte cultures were taken from the cerebral and cerebellar cortices of wild (WT), hetero (HE), and knock-out (KO) mice. Major gliotransmitters were analyzed using high-performance liquid chromatography. It was observed that the amount of excitatory and inhibitory gliotransmitters were dependent on genotype and showed a change in excitation/inhibition ratios. Interestingly, the major excitatory gliotransmitter, glutamate, existed at the lowest level in WT mice, but the amount of inhibitory gliotransmitters, gamma-aminobutyric acid (GABA) and glycine, varied depending on brain region. Remarkably, an increased amount of GABA was measured at the intracellular cerebrum in WT mice compared with KO mice. It was presumed that KO mice would secrete more inhibitory gliotransmitters to compensate for GIT1 depletion or else acquire a defect to reuptake-secreted GABA. This may be a possible mechanism for ADHD pathology.