Ashwagandha Diminishes Hippocampal Apoptosis Induced by Microwave Radiation by Acetylcholinesterase Dependent Neuro-Inflammatory Pathway in Male Coturnix coturnix Japonica.

Microwave radiation (MWR) has been linked to neurodegeneration by inducing oxidative stress in the hippocampus of brain responsible for learning and memory. Ashwagandha (ASW), a medicinal plant is known to prevent neurodegeneration and promote neuronal health. This study investigated the effects of MWR and ASW on oxidative stress and cholinergic imbalance in the hippocampus of adult male Japanese quail. One control group received no treatment, the second group quails were exposed to MWR at 2 h/day for 30 days, third was administered with ASW root extract orally 100 mg/day/kg body weight and the fourth was exposed to MWR and also treated with ASW. The results showed that MWR increased serum corticosterone levels, disrupted cholinergic balance and induced neuro-inflammation. This neuro-inflammation further led to oxidative stress, as evidenced by decreased activity of antioxidant enzymes SOD, CAT and GSH. MWR also caused a significant decline in the nissil substances in the hippocampus region of brain indicating neurodegeneration through oxidative stress mediated hippocampal apoptosis. ASW, on the other hand, was able to effectively enhance the cholinergic balance and subsequently lower inflammation in hippocampus neurons. This suggests that ASW can protect against the neurodegenerative effects of MWR. ASW also reduced excessive ROS production by increasing the activity of ROS-scavenging enzymes. Additionally, ASW prevented neurodegeneration through decreased expression of caspase-3 and caspase-7 in hippocampus, thus promoting neuronal health. In conclusion, this study showed that MWR induces apoptosis and oxidative stress in the brain, while ASW reduces excessive ROS production, prevents neurodegeneration and promotes neuronal health.

Exposure to 2.45 GHz Radiation Triggers Changes in HSP-70, Glucocorticoid Receptors and GFAP Biomarkers in Rat Brain.

Brain tissue may be especially sensitive to electromagnetic phenomena provoking signs of neural stress in cerebral activity. Fifty-four adult female Sprague-Dawley rats underwent ELISA and immunohistochemistry testing of four relevant anatomical areas of the cerebrum to measure biomarkers indicating induction of heat shock protein 70 (HSP-70), glucocorticoid receptors (GCR) or glial fibrillary acidic protein (GFAP) after single or repeated exposure to 2.45 GHz radiation in the experimental set-up. Neither radiation regime caused tissue heating, so thermal effects can be ruled out. A progressive decrease in GCR and HSP-70 was observed after acute or repeated irradiation in the somatosensory cortex, hypothalamus and hippocampus. In the limbic cortex; however, values for both biomarkers were significantly higher after repeated exposure to irradiation when compared to control animals. GFAP values in brain tissue after irradiation were not significantly different or were even lower than those of nonirradiated animals in all brain regions studied. Our results suggest that repeated exposure to 2.45 GHz elicited GCR/HSP-70 dysregulation in the brain, triggering a state of stress that could decrease tissue anti-inflammatory action without favoring glial proliferation and make the nervous system more vulnerable.

Neurobehavioral effects of acute low-dose whole-body irradiation.

Radiation exposure has multiple effects on the brain, behavior and cognitive functions. It has been reported that high-dose (>20 Gy) radiation-induced behavior and cognitive aberration partly associated with severe tissue destruction. Low-dose (<3 Gy) exposure can occur in radiological disasters and cerebral endovascular treatment. However, only a few reports analyzed behavior and cognitive functions after low-dose irradiation. This study was undertaken to assess the relationship between brain neurochemistry and behavioral disruption in irradiated mice. The irradiated mice (0.5 Gy, 1 Gy and 3 Gy) were tested for alteration in their normal behavior over 10 days. A serotonin (5-HT), Dopamine, gamma-Aminobutyric acid (GABA) and cortisol analysis was carried out in blood, hippocampus, amygdala and whole brain tissue. There was a significant decline in the exploratory activity of mice exposed to 3 Gy and 1 Gy radiation in an open field test. We observed a significant short-term memory loss in 3 Gy and 1 Gy irradiated mice in Y-Maze. Mice exposed to 1 Gy and 3 Gy radiation exhibited increased anxiety in an elevated plus maze (EPM). The increased anxiety and memory loss patterns were also seen in 0.5 Gy irradiated mice, but the results were not statistically significant. In this study we observed that neurotransmitters are significantly altered after irradiation, but the neuronal cells in the hippocampus were not significantly affected. This study suggests that the low-dose radiation-induced cognitive impairment may be associated with the neurochemical in low-dose irradiation and unlike the high-dose scenario might not be directly related to the morphological changes in the brain.

Gut flora-targeted photobiomodulation therapy improves senile dementia in an Aß-induced Alzheimer's disease animal model.

BACKGROUND: Emerging evidence suggests that the gut microbiota plays an important role in the pathological progression of Alzheimer's disease (AD). Photobiomodulation (PBM) therapy is believed to have a positive regulatory effect on the imbalance of certain body functions, including inflammation, immunity, wound healing, nerve repair, and pain. Previous studies have found that the intestinal flora of patients with AD is in an unbalanced state. Therefore, we have proposed the use of gut flora-targeted PBM (gf-targeted PBM) as a method to improve AD in an Aß-induced AD mouse model. METHODS: PBM was performed on the abdomen of the mice at the wavelengths of 630 nm, 730 nm, and 850 nm at 100 J/cm2 for 8 weeks. Morris water maze test, immunofluorescence and proteomic of hippocampus, and intestinal flora detection of fecal were used to evaluate the treatment effects of gf-targeted PBM on AD rats. RESULTS: PBM at all three wavelengths (especially 630 nm and 730 nm) significantly improved learning retention as measured by the Morris water maze. In addition, we found reduced amyloidosis and tau phosphorylation in the hippocampus by immunofluorescence in AD mice. By using a quantitative proteomic analysis of the hippocampus, we found that gf-targeted PBM significantly altered the expression levels of 509 proteins (the same differentially expressed proteins in all three wavelengths of PBM), which involved the pathways of hormone synthesis, phagocytosis, and metabolism. The 16 s rRNA gene sequencing of fecal contents showed that PBM significantly altered the diversity and abundance of intestinal flora. Specifically, PBM treatment reversed the typical increase of Helicobacter and uncultured Bacteroidales and the decrease of Rikenella seen in AD mice. CONCLUSIONS: Our data indicate that gf-targeted PBM regulates the diversity of intestinal flora, which may improve damage caused by AD. Gf-targeted PBM has the potential to be a noninvasive microflora regulation method for AD patients.

Effects of prenatal photobiomodulation treatment on neonatal hypoxic ischemia in rat offspring.

Neonatal hypoxic-ischemic (HI) injury is a severe complication often leading to neonatal death and long-term neurobehavioral deficits in children. Currently, the only treatment option available for neonatal HI injury is therapeutic hypothermia. However, the necessary specialized equipment, possible adverse side effects, and limited effectiveness of this therapy creates an urgent need for the development of new HI treatment methods. Photobiomodulation (PBM) has been shown to be neuroprotective against multiple brain disorders in animal models, as well as limited human studies. However, the effects of PBM treatment on neonatal HI injury remain unclear. Methods: Two-minutes PBM (808 nm continuous wave laser, 8 mW/cm2 on neonatal brain) was applied three times weekly on the abdomen of pregnant rats from gestation day 1 (GD1) to GD21. After neonatal right common carotid artery ligation, cortex- and hippocampus-related behavioral deficits due to HI insult were measured using a battery of behavioral tests. The effects of HI insult and PBM pretreatment on infarct size; synaptic, dendritic, and white matter damage; neuronal degeneration; apoptosis; mitochondrial function; mitochondrial fragmentation; oxidative stress; and gliosis were then assessed. Results: Prenatal PBM treatment significantly improved the survival rate of neonatal rats and decreased infarct size after HI insult. Behavioral tests revealed that prenatal PBM treatment significantly alleviated cortex-related motor deficits and hippocampus-related memory and learning dysfunction. In addition, mitochondrial function and integrity were protected in HI animals treated with PBM. Additional studies revealed that prenatal PBM treatment significantly alleviated HI-induced neuroinflammation, oxidative stress, and myeloid cell/astrocyte activation. Conclusion: Prenatal PBM treatment exerts neuroprotective effects on neonatal HI rats. Underlying mechanisms for this neuroprotection may include preservation of mitochondrial function, reduction of inflammation, and decreased oxidative stress. Our findings support the possible use of PBM treatment in high-risk pregnancies to alleviate or prevent HI-induced brain injury in the perinatal period.

Sparing the hippocampus and the hypothalamic- pituitary region during whole brain radiotherapy: a volumetric modulated arc therapy planning study.

BACKGROUND: Feasibility testing of a simultaneous sparing approach of hippocampus, hypothalamus and pituitary gland in patients undergoing whole-brain radiotherapy (WBRT) with and without a concomitant boost to metastatic sites. INTRODUCTION: Cognitive impairment and hormonal dysfunction are common side effects of cranial radiotherapy. A reduced dose application to the patho-physiologically involved functional brain areas, i.e. hippocampus, hypothalamus and pituitary gland, could reduce these common side effects. While hippocampal sparing is already a common practice to improve cognitive outcome, technical experience of additional combined sparing of the hypothalamus/pituitary gland (HT-P) is insufficient. METHODS: Twenty patients were included in the planning study. In 11 patients, a total dose of 36 Gy of WBRT (2 Gy per fraction) plus a simultaneous integrated boost (SIB) of 9 Gy (0.5 Gy per fraction, total dose: 45 Gy) to the brain metastases was applied. In 9 patients, prophylactic cranial irradiation (PCI) was simulated with a total dose of 30 Gy (2 Gy per fraction). In both patient cohorts, a sparing approach of the hippocampus and the HT-P area was simulated during WBRT. For all treatment plans, volumetric modulated arc therapy (VMAT) was used. Quality assurance included assessment of homogeneity, conformality and target coverage. RESULTS: The mean dose to the hippocampus and HT-P region was limited to less than 50% of the prescribed dose to the planning target volume (PTV) in all treatment plans. Dose homogeneity (HI) of the target volume was satisfying (median HI = 0.16 for WBRT+SIB and 0.1 for PCI) and target coverage (conformation number, CN) was not compromised (median CN = 0.82 for SIB and 0.86 for PCI). CONCLUSION: Simultaneous dose reduction to the hippocampus and the HT-P area did not compromise the PTV coverage in patients undergoing WBRT+SIB or PCI using VMAT. While the feasibility of the presented approach is promising, prospective neurologic, endocrine outcome and safety studies are required.

Electroacupuncture Pretreatment Alleviates Cerebral Ischemia-Reperfusion Injury by Increasing GSK-3ß Phosphorylation Level via Adenosine A1 Receptor.

OBJECTIVE: To observe the effect of adenosine A1 receptor in the hippocampus of mice on GSK-3ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury. METHOD: The model of middle cerebral artery occlusion (MCAO) was established and grouped into electroacupuncture pretreatment group (EA group), MCAO group, and sham-operated group (Sham group). The neurobehavioral manifestation, the volume of cerebral infarction, and its related protein changes in mice in each group were observed. Then, adenosine Α1 receptor antagonist and agonist were injected intraperitoneally to observe the effects of A1 receptor on the phosphorylation level of GSK-3ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury. RESULTS: (1) Compared with the MCAO group (24 hours after reperfusion), the infarct size in the EA group decreased significantly, and the Garcia neurological score and phosphorylation level of GSK-3ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury. ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury. ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury. CONCLUSIONS: Electroacupuncture pretreatment can increase GSK-3ß phosphorylation level via activating A1 receptor, to protect neurons in ischemia-reperfusion injury.ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury.

[Effects and mechanisms of electro-acupuncture on proliferation and differentiation of neural stem cells in C57 mice exposed to different doses of X-ray radiation].

The present study was aimed to investigate the effects and mechanisms of electro-acupuncture (EA) on proliferation and differentiation of neural stem cells in the hippocampus of C57 mice exposed to different doses of X-ray radiation. Thirty-day-old C57BL/6J mice were randomly divided into control, irradiation, and EA groups. The control group was not treated with irradiation. The irradiation groups were exposed to different doses of X-ray (4, 8 or 16 Gy) for 10 min. The EA groups were electro-acupunctured at Baihui, Fengfu and bilateral Shenyu for 3 courses of treatment after X-ray radiation. Immunohistochemistry was used to evaluate proliferation and differentiation of the hippocampal neural stem cell. RT-PCR and Western blot were used to detect mRNA and protein expressions of Notch1 and Mash1 in the hippocampus, respectively. The results showed that, compared with the control group, the numbers of BrdU positive cells (4, 8 Gy subgroup) and BrdU/NeuN double-labeling positive cells (3 dose subgroups) were decreased significantly in the irradiation group, but the above changes could be reversed by EA. Compared with the control group, the number of BrdU/GFAP double-labeling positive cells in each dose subgroup of irradiation group was decreased significantly, while EA could reverse the change of 4 and 8 Gy dose subgroups. In addition, compared with the control group, the expression levels of Notch1 mRNA and protein in hippocampus were up-regulated, and the expression levels of Mash1 mRNA and protein were significantly decreased in each dose subgroup of irradiation group. Compared with irradiation group, the expression levels of Notch1 mRNA and protein in hippocampus of EA group were decreased significantly in each dose subgroup, and the expression levels of Mash1 mRNA and protein were increased significantly in 4 and 8 Gy subgroups. These results suggest that irradiation affects the proliferation and differentiation of neural stem cells in hippocampus of mice, whereas EA may significantly increase the proliferation and differentiation of hippocampal neural stem cells via the regulation of Notch signaling pathway.

Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study.

BACKGROUND: Hippocampal avoidance has been suggested as a strategy to reduce short-term memory decline in adults receiving whole-brain radiation therapy (RT). The purpose of this study was to determine whether the hippocampal dose in children and adolescents undergoing RT for low-grade glioma was associated with memory, as measured by verbal recall. METHODS: Eighty patients aged at least 6 years but less than 21 years with low-grade glioma were treated with RT to 54 Gy on a phase II protocol. Patients underwent age-appropriate cognitive testing at baseline, 6 months posttreatment, yearly through 5 years posttreatment, year 7 or 8, and year 10 posttreatment. Random coefficient models were used to estimate the longitudinal trends in cognitive assessment scores. RESULTS: Median neurocognitive follow-up was 9.8 years. There was a significant decline in short-delay recall (slope = -0.01 standard deviation [SD]/year, P < 0.001), total recall (slope = -0.09 SD/y, P = 0.005), and long-delay recall (slope = -0.01 SD/y, P = 0.002). On multivariate regression, after accounting for hydrocephalus, decline in short-delay recall was associated with the volume of right (slope = -0.001 SD/y, P = 0.019) or left hippocampus (slope = -0.001 SD/y, P = 0.025) receiving 40 Gy (V40 Gy). On univariate regression, decline in total recall was only associated with right hippocampal dosimetry (V40 Gy slope = -0.002, P = 0.025). In children <12 years, on univariate regression, decline in long-delay recall was only associated with right (V40 Gy slope = -0.002, P = 0.013) and left (V40 Gy slope = -0.002, P = 0.014) hippocampal dosimetry. CONCLUSION: In this 10-year longitudinal study, greater hippocampal dose was associated with a greater decline in delayed recall. Such findings might be informative for radiation therapy planning, warranting prospective evaluation.

Optimized neuron models for estimation of charged particle energy deposition in hippocampus.

The study of evaluating radiation risk on the central nervous system induced by space-born charged particles is very complex and challenging task in space radiobiology and radiation protection. To overcome computational difficulties in this field, we developed simplified neuron models with properties equivalent to realistic neuron morphology. Three-dimensional structure and parameters of simplified and complex neuron models with realistic morphology were obtained from the experimental data. The models implement uniform random distribution of spines along the dendritic branches in typical hippocampal neurons. Both types of models were implemented and tested using Geant4 Monte Carlo radiation transport code. Track structure simulations were performed for ion beams with typical fluxes of galactic cosmic rays expected for long-term interplanetary missions. The distribution of energy deposition events and percentage of irradiated volumes were obtained to be similar in both simplified and realistic models of pyramidal and granule cells of the rat hippocampus following irradiation. Significant increase of computational efficiency for detailed microdosimetry simulations of hippocampus using simplified neuron models was achieved. Using designed neuron models we have constructed 3D model of the rat hippocampus, including pyramidal cells, mature and immature granular cells, mossy cells, and neural stem cells. Computed energy deposition in irradiated hippocampal neurons following a track of iron ion suggests that most of energy is accumulated by dense population of granular cells in the dentate gyrus. Proposed approach could serve as a complementary computation technique for studying radiation-induced effects in large scale brain networks.

Photobiomodulation for Global Cerebral Ischemia: Targeting Mitochondrial Dynamics and Functions.

Hypothermia is currently the only approved therapy for global cerebral ischemia (GCI) after cardiac arrest; however, it unfortunately has multiple adverse effects. As a noninvasive procedure, photobiomodulation (PBM) therapy has emerged as a potential novel treatment for brain injury. PBM involves the use of low-level laser light therapy to influence cell behavior. In this study, we evaluated the therapeutic effects of PBM treatment with an 808-nm diode laser initiated 6 h after GCI. It was noted that PBM dose-dependently protected against GCI-induced neuronal death in the vulnerable hippocampal CA1 subregion. Functional assessments demonstrated that PBM markedly preserved both short-term (a week) and long-term (6 months) spatial learning and memory function following GCI. Further mechanistic studies revealed that PBM post-treatment (a) preserved healthy mitochondrial dynamics and suppressed substantial mitochondrial fragmentation of CA1 neurons, by reducing the detrimental Drp1 GTPase activity and its interactions with adaptor proteins Mff and Fis1 and by balancing mitochondrial targeting fission and fusion protein levels; (b) reduced mitochondrial oxidative damage and excessive mitophagy and restored mitochondrial overall health status and preserved mitochondrial function; and (c) suppressed mitochondria-dependent apoptosome formation/caspase-3/9 apoptosis-processing activities. Additionally, we validated, in an in vitro ischemia model, that cytochrome c oxidase served as a key PBM target for mitochondrial function preservation and neuroprotection. Our findings suggest that PBM serves as a promising therapeutic strategy for the functional recovery after GCI, with mechanisms involving PBM's preservation on mitochondrial dynamics and functions and the inhibition of delayed apoptotic neuronal death in GCI.

A Protocol for Transcranial Photobiomodulation Therapy in Mice.

Transcranial photobiomodulation is a potential innovative noninvasive therapeutic approach for improving brain bioenergetics, brain function in a wide range of neurological and psychiatric disorders, and memory enhancement in age-related cognitive decline and neurodegenerative diseases. We describe a laboratory protocol for transcranial photobiomodulation therapy (PBMT) in mice. Aged BALB/c mice (18 months old) are treated with a 660 nm laser transcranially, once daily for 2 weeks. Laser transmittance data shows that approximately 1% of the incident red light on the scalp reaches a 1 mm depth from the cortical surface, penetrating the dorsal hippocampus. Treatment outcomes are assessed by two methods: a Barnes maze test, which is a hippocampus-dependent spatial learning and memory task evaluation, and measuring hippocampal ATP levels, which is used as a bioenergetics index. The results from the Barnes task show an enhancement of the spatial memory in laser-treated aged mice when compared with age-matched controls. Biochemical analysis after laser treatment indicates increased hippocampal ATP levels. We postulate that the enhancement of memory performance is potentially due to an improvement in hippocampal energy metabolism induced by the red laser treatment. The observations in mice could be extended to other animal models since this protocol could potentially be adapted to other species frequently used in translational neuroscience, such as rabbit, cat, dog, or monkey. Transcranial photobiomodulation is a safe and cost-effective modality which may be a promising therapeutic approach in age-related cognitive impairment.

Modulating effects of on-line low frequency electromagnetic fields on hippocampal long-term potentiation in young male Sprague-Dawley rat.

The low frequency electromagnetic fields (LF-EMFs) are attracting more attention and studied deeply because of their effects on human health and biology. Recent reports indicate that exposure of rats to LF-EMFs induces persistent changes in neuronal activity. The studies used the following standard methods: the rats or rat brain slices were first stimulated in an external electromagnetic exposure system, and then moved to a patch clamp perfusion chamber to record electrophysiological characteristics (off-line magnetic exposure). However, this approach is susceptible to many disturbances, such as the effects of brain slice movements. In this paper, we describe a novel patch-clamp setup which is modified to allow accurate on-line LF-EMFs stimulation. We performed the computational simulations of the stimulation coils to describe the uniformity of the distribution of the on-line magnetic field. The 0.5, 1, 2 mT magnetic field of 15 Hz, 50 Hz, and 100 Hz was produced and applied to slices to study the effect of LF-EMFs on synaptic plasticity. We demonstrated that the slope of field excitatory postsynaptic potentials (fEPSPs) decreased significantly under the priming on-line uninterrupted or pulsed sinusoidal LF-EMFs stimulation. In the present study, we investigated whether LF-EMFs can induce long-term potentiation (LTP) in male Sprague-Dawley rat hippocampal slices in vitro. Interestingly, these results highlight the role of 100 Hz pulsed sinusoidal LF-EMFs only as a modulator, rather than an LTP inducer.

Monitoring the Opening and Recovery of the Blood-Brain Barrier with Noninvasive Molecular Imaging by Biodegradable Ultrasmall Cu2- xSe Nanoparticles.

The reversible and controllable opening and recovery of the blood-brain barrier (BBB) is crucial for the treatment of brain diseases, and it is a big challenge to noninvasively monitor these processes. In this article, dual-modal photoacoustic imaging and single-photon-emission computed tomography imaging based on ultrasmall Cu2- xSe nanoparticles (3.0 nm) were used to noninvasively monitor the opening and recovery of the BBB induced by focused ultrasound in living mice. The ultrasmall Cu2- xSe nanoparticles were modified with poly(ethylene glycol) to exhibit a long blood circulation time. Both small size and long blood circulation time enable them to efficiently penetrate into the brain with the assistance of ultrasound, which resulted in a strong signal at the sonicated site and allowed for photoacoustic and single-photon emission computed tomography imaging monitoring the recovery of the opened BBB. The results of biodistribution, blood routine examination, and histological staining indicate that the accumulated Cu2- xSe nanoparticles could be excreted from the brain and other major organs after 15 days without causing side effects. By the combination of the advantages of noninvasive molecular imaging and focused ultrasound, the ultrasmall biocompatible Cu2- xSe nanoparticles holds great potential for the diagnosis and therapeutic treatment of brain diseases.

Light-Emitting Diode (LED) Therapy Attenuates Neurotoxicity of Methanol-Induced Memory Impairment and Apoptosis in The Hippocampus.

BACKGROUND & OBJECTIVE: The adolescent brain has a higher vulnerability to alcoholinduced neurotoxicity, compared to adult's brain. Most studies have investigated the effect of ethanol consumption on the body, however, methanol consumption, which peaked in the last years, is still poorly explored. METHOD: In this study, we investigated the effects of methanol neurotoxicity on memory function and pathological outcomes in the hippocampus of adolescent rats and examined the efficacy of Light- Emitting Diode (LED) therapy. Methanol induced neurotoxic rats showed a significant decrease in the latency period, in comparison to controls, which was significantly improved in LED treated rats at 7, 14 and 28 days, indicating recovery of memory function. In addition, methanol neurotoxicity in hippocampus caused a significant increase in cell death (caspase3+ cells) and cell edema at 7 and 28 days, which were significantly decreased by LED therapy. Furthermore, the number of glial fibrillary acid protein astrocytes was significantly lower in methanol rats, compared to controls, whereas LED treatment caused their significant increase. Finally, methanol neurotoxicity caused a significant decrease in the number of brain-derived neurotrophic factor (BDNF+) cells, but also circulating serum BDNF, at 7 and 28 days, compared to controls, which were significantly increased by LED therapy. Importantly, LED significantly increased the number of Ki-67+ cells and BDNF levels in the serum and hypothalamus in control-LED rats, compared to controls without LED therapy. CONCLUSION: In conclusion, chronic methanol administration caused severe memory impairments and several pathological outcomes in the hippocampus of adolescent rats which were improved by LED therapy.

Histopathological, immunohistochemical, and stereological analysis of the effect of Ginkgo biloba (Egb761) on the hippocampus of rats exposed to long-term cellphone radiation.

Cellular phones are major sources of electromagnetic radiation (EMR) that can penetrate the human body and pose serious health hazards. The increasingly widespread use of mobile communication systems has raised concerns about the effects of cellphone radiofrequency (RF) on the hippocampus because of its close proximity to radiation during cellphone use. The effects of cellphone EMR exposure on the hippocampus of rats and the possible counteractive effects of Ginkgo biloba (Egb761) were aimed to investigate. Rats were divided into three groups: Control, EMR, and EMR+Egb761. The EMR and EMR+Egb761 groups were exposed to cellphone EMR for one month. Egb761 was also administered to the EMR+Egb761 group. Specifically, we evaluated the effect of RF exposure on rat hippocampi at harmful EMR levels (0.96 W/kg specific absorption rate [SAR]) for one month and also investigated the possible impact of Ginkgo biloba (Egb761) using stereological, TUNEL-staining, and immunohistochemical methods. An increase in apoptotic proteins (Bax, Acas-3) and a decrease in anti-apoptotic protein (Bcl-2) immunoreactivity along with a decrease in the total granule and pyramidal cell count were noted in the EMR group. A decrease in Bax and Acas-3 and an increase in Bcl-2 immunoreactivity were observed in rats treated with Egb761 in addition to a decrease in TUNEL-stained apoptotic cells and a higher total viable cell number. In conclusion, chronic cellphone EMR exposure may affect hippocampal cell viability, and Egb761 may be used to mitigate some of the deleterious effects.

Influence of extremely low frequency magnetic fields on Ca2+ signaling and double messenger system in mice hippocampus and reversal function of procyanidins extracted from lotus seedpod.

This research investigated the influence of extremely low frequency magnetic fields (ELF-MF; 50 Hz, 8 mT, 4 h per day, for 28 days) on calcium ion signaling and the double messenger system in the hippocampus of mice. Messengers that were studied included: G-protein, Ins(1,4,5)P3 (IP3 ), diacylglycerol (DAG), cAMP-dependent protein kinase (PKA), and Ca2+ -dependent protein kinase C (PKC). The results showed that ELF-MF caused an increase in the levels of Gi protein, IP3, DAG, PKA and PKC beta, calcium and calmodulin-dependent protein phosphatase calcineuring (PP2B), and intracellular Ca2+ content, and a decrease in calcium/calmodulin-dependent protein kinase II (CaMK II) and PKC alpha. In addition, ELF-MF exposure decreased the level of brain-derived neurotrophic factor (BDNF), which played a key role in hippocampal neuronal cell death. However, oral administration of procyanidins from lotus seedpod (LSPCs) (especially 90 mg kg-1 ) significantly recovered these changes, and nearly reached normal levels. All these showed that LSPCs may mediate calcium signal and double messenger system through Ca2+ /CaMK II/CREB/BDNF and DG/PKC/MAPK signaling pathways to reverse the alteration caused by ELF-MF. Bioelectromagnetics. 38:436-446, 2017. © 2017 Wiley Periodicals, Inc.

A standardized Hippophae extract (SBL-1) counters neuronal tissue injuries and changes in neurotransmitters: implications in radiation protection.

CONTEXT: Effects of a radioprotective, standardized leaf extract (code SBL-1) from traditional medicinal plant, sea buckthorn [Hippophae rhamnoides L. (Elaeagnaceae)], on neurotransmitters and brain injuries in rats showing radiation-induced conditioned taste aversion (CTA), are not known. Understanding CTA in rats is important because its process is considered parallel to nausea and vomiting in humans. OBJECTIVE: This study investigated the levels of neurotransmitters, antioxidant defences and histological changes in rats showing radiation CTA, and their modification by SBL-1. MATERIALS AND METHODS: The inbred male Sprague-Dawley rats (age 65 days, weighing 190 ± 10 g) were used. Saccharin-preferring rats were selected using standard procedure and divided into groups. Group I (untreated control) was administered sterile water, group II was 60Co-γ-irradiated (2 Gy), and group III was administered SBL-1 before irradiation. Observations were recorded up to day 5. RESULTS: Irradiation (2 Gy) caused (i) non-recoverable CTA (≥ 64.7 ± 5.0%); (ii) degenerative changes in cerebral cortex, amygdala and hippocampus; (iii) increases in brain dopamine (DA, 63.4%), norepinephrine (NE, 157%), epinephrine (E, 233%), plasma NE (103%) and E (160%); and (iv) decreases in brain superoxide dismutase (67%), catalase (60%) and glutathione (51%). SBL-1 treatment (12 mg/kg body weight) 30 min before irradiation (i) countered brain injuries, (ii) reduced CTA (38.7 ± 3.0%, day 1) and (iii) normalized brain DA, NE, E, superoxide dismutase, catalase and CTA from day 3 onwards. DISCUSSION AND CONCLUSION: Radiation CTA was coupled with brain injuries, disturbances in neurotransmitters and antioxidant defences. SBL-1 pretreatment countered these disturbances, indicating neuroprotective action.

Electroacupuncture Improves Cognitive Function and Hippocampal Neurogenesis after Brain Irradiation.

Cognitive impairments after brain irradiation seriously affect quality of life for patients, and there is currently no effective treatment. In this study using an irradiated rat model, the role of electroacupuncture was investigated for treatment of radiation-induced brain injury. Animals received 10 Gy exposure to the entire brain, and electroacupuncture was administered 3 days before irradiation as well as up to 2 weeks postirradiation. Behavioral tests were performed one month postirradiation, and rats were then sacrificed for histology or molecular studies. Electroacupuncture markedly improved animal performance in the novel place recognition test. In the emotion test, electroacupuncture reduced defecation during the open-field test, and latency to consumption of food in the novelty suppressed feeding test. Brain irradiation inhibited the generation of immature neurons, but did not cause neural stem cell loss. Electroacupuncture partially restored hippocampal neurogenesis. Electroacupuncture decreased the amount of activated microglia and increased resting microglia in the hippocampus after irradiation. In addition, electroacupuncture promoted mRNA and protein expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In conclusion, electroacupuncture could improve cognitive function and hippocampal neurogenesis after irradiation, and the protective effect of electroacupuncture was associated with the modulation of microglia and upregulation of BDNF in the hippocampus.

Transcranial LED therapy on amyloid-ß toxin 25-35 in the hippocampal region of rats.

Excessive Aß deposition in the brain is associated with the formation of senile plaques, and their diffuse distribution is related to Alzheimer's disease. Thirty rats (EG) were irradiated with light-emitting diode (photobiomodulation (PBM)) in the frontal region of the skull after being inoculated with the Aß toxin in the hippocampus; 30 rats were used as the control group (CG). The analysis was conducted at 7, 14, and 21 days after irradiation. We observed a decreased in Aß deposits in treated animals compared with animals in the CG. The behavioral and motor assessment revealed that the EG group covered a larger ground distance and explored the open field than the CG group on days 14 and 21 (p < 0.05). The EG group was statistically significant in the spatial memory test compared to the CG group on day 14. The use of PBM significantly reduced the presence of Aß plaques and improved spatial memory and behavioral and motor skills in treated animals on day 21.