scholarly journals Combination of Matching Responsive Stimulations of Hippocampus and Subiculum for Effective Seizure Suppression in Temporal Lobe Epilepsy

2021 ◽  
Vol 12 ◽  
Author(s):  
Fang Zhang ◽  
Yufang Yang ◽  
Yongte Zheng ◽  
Junming Zhu ◽  
Ping Wang ◽  
...  

Responsive neural stimulation (RNS) is considered a promising neural modulation therapy for refractory epilepsy. Combined stimulation on different targets may hold great promise for improving the efficacy of seizure control since neural activity changed dynamically within associated brain targets in the epileptic network. Three major issues need to be further explored to achieve better efficacy of combined stimulation: (1) which nodes within the epileptogenic network should be chosen as stimulation targets? (2) What stimulus frequency should be delivered to different targets? and (3) Could the efficacy of RNS for seizure control be optimized by combined different stimulation targets together? In our current study, Granger causality (GC) method was applied to analyze epileptogenic networks for finding key targets of RNS. Single target stimulation (100 μA amplitude, 300 μs pulse width, 5s duration, biphasic, charge-balanced) with high frequency (130 Hz, HFS) or low frequency (5 Hz, LFS) was firstly delivered by our lab designed RNS systems to CA3, CA1, subiculum (SUB) of hippocampi, and anterior nucleus of thalamus (ANT). The efficacy of combined stimulation with different groups of frequencies was finally assessed to find out better combined key targets with optimal stimulus frequency. Our results showed that stimulation individually delivered to SUB and CA1 could shorten the average duration of seizures. Different stimulation frequencies impacted the efficacy of seizure control, as HFS delivered to CA1 and LFS delivered to SUB, respectively, were more effective for shortening the average duration of electrographic seizure in Sprague-Dawley rats (n = 3). Moreover, the synchronous stimulation of HFS in CA1 combined with LFS in SUB reduced the duration of discharge significantly in rats (n = 6). The combination of responsive stimulation at different targets may be an inspiration to optimize stimulation therapy for epilepsy.

Author(s):  
Min Hu ◽  
Fan Du ◽  
Shi Liu

The purpose of this study was to investigate the effects of electroacupuncture at Zusanli acupoint on the enteric neuropathy in diabetic rats. Sprague–Dawley rats were divided into different groups depending on the total electroacupuncture span and frequency. The expression of nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5 (PGP9.5), and doublecortin was significantly decreased in the diabetic group compared with the control group. Long-term electroacupuncture at Zusanli with either high frequency or low frequency could increase the expression levels of nNOS, CHAT, PGP9.5, and doublecortin, and the increase was greater in the high-frequency group. But no obvious changes were seen in the short-term electroacupuncture groups. These results suggest that electroacupuncture at Zusanli can restore the deficiency of enteric neurons in diabetes partly but a comparative long duration of stimuli (6 weeks) is required. The increase of doublecortin may be involved in this positive process.


2017 ◽  
pp. 449-457 ◽  
Author(s):  
Y.-H. LIN ◽  
Y.-P. LIU ◽  
Y.-C. LIN ◽  
P.-L. LEE ◽  
C.-S. TUNG

This study extends our previous work by examining the effects of alpha2-adrenoceptors under cold stimulation involving the increase of myogenic vascular oscillations as increases of very-low-frequency and low-frequency of the blood pressure variability. Forty-eight adult male Sprague-Dawley rats were randomly divided into four groups: vehicle; yohimbine; hexamethonium+yohimbine; guanethidine+yohimbine. Systolic blood pressure, heart rate, power spectral analysis of spontaneous blood pressure and heart rate variability and spectral coherence at very-low-frequency (0.02 to 0.2 Hz), low-frequency (0.2 to 0.6 Hz), and high-frequency (0.6 to 3.0 Hz) regions were monitored using telemetry. Key findings are as follows: 1) Cooling-induced pressor response was attenuated by yohimbine and further attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 2) Cooling-induced tachycardia response of yohimbine was attenuated by hexame-thonium+yohimbine and guanethidine+yohimbine, 3) Different patterns of power spectrum reaction and coherence value compared hexamethonium+yohimbine and guanethi-dine+yohimbine to yohimbine alone under cold stimulation. The results suggest that sympathetic activation of the postsynaptic alpha2-adrenoceptors causes vasoconstriction and heightening myogenic vascular oscillations, in turn, may increase blood flow to prevent tissue damage under stressful cooling challenge.


2002 ◽  
Vol 93 (6) ◽  
pp. 2192-2198 ◽  
Author(s):  
Robert P. Carson ◽  
André Diedrich ◽  
David Robertson

Orthostatic intolerance is a debilitating syndrome characterized by tachycardia on assumption of upright posture. The norepinephrine (NE) transporter (NET) has been implicated in a genetic form of the disorder. We assessed the combined central and peripheral effects of pharmacological NET blockade on cardiovascular regulation and baroreflex sensitivity in rats. NE reuptake was blocked chronically in female Sprague-Dawley rats by the NET antagonist desipramine (DMI). Treated animals demonstrated an elevated supine heart rate, reduced tyramine responsiveness, and a reduced plasma ratio of the intraneuronal NE metabolite dihydroxyphenylglycol relative to NE, all of which are consistent with observations in human NET deficiency. Spectral analysis revealed a dramatic decrease in low-frequency spectral power after DMI that was consistent with decreased sympathetic outflow. Stimulation of the baroreflex with the vasodilator nitroprusside revealed an attenuated tachycardia in DMI-treated animals. This indicated that the DMI-induced sympathoinhibitory effects of increased NE in the brain stem predominates over the functional elevation of NE stimulation of peripheral targets. Thus attenuated baroreflex function and reduced sympathetic outflow may contribute to the orthostatic intolerance of severe NET deficiency.


2004 ◽  
Vol 4 ◽  
pp. 91-99 ◽  
Author(s):  
Daniela Quaglino ◽  
Miriam Capri ◽  
Luigi Zecca ◽  
Claudio Franceschi ◽  
Ivonne P. Ronchetti

Thymus plays an important role in the immune system and can be modulated by numerous environmental factors, including electromagnetic fields (EMF). The present study has been undertaken with the aim to investigate the role of long-term exposure to extremely low frequency electric and magnetic fields (ELF-EMF) on thymocytes of rats housed in a regular dark/light cycle or under continuous light. Male Sprague-Dawley rats, 2 months old, were exposed or sham exposed for 8 months to 50-Hz sinusoidal EMF at two levels of field strength (1 kV/m, 5 μT and 5 kV/m, 100 μT, respectively). Thymus from adult animals exhibits signs of gradual atrophy mainly due to collagen deposition and fat substitution. This physiological involution may be accelerated by continuous light exposure that induces a massive death of thymocytes. The concurrent exposure to continuous light and to ELF-EMF did not change significantly the rate of mitoses compared to sham-exposed rats, whereas the amount of cell death was significantly increased, also in comparison with animals exposed to EMF in a 12-h dark-light cycle. In conclusion, long-term exposure to ELF-EMF, in animals housed under continuous light, may reinforce the alterations due to a photic stress, suggesting that,in vivo, stress and ELF-EMF exposure can act in synergy determining a more rapid involution of the thymus and might be responsible for an increased susceptibility to the potentially hazardous effects of ELF-EMF.


2010 ◽  
Vol 298 (1) ◽  
pp. F118-F124 ◽  
Author(s):  
Zhongguang Yang ◽  
Paul C. Dolber ◽  
Matthew O. Fraser

Urethral reflexes are important regulators of micturition, and impairment of urethral afferent neuronal function may disrupt coordinated bladder and urethral activity, thereby contributing to voiding dysfunction in lower urinary tract disorders. Chemical stimulation by intraurethral irritant solution perfusion was used to determine whether urethral afferent neuronal function is altered in diabetes mellitus (DM). Sprague-Dawley rats were studied 10 wk after streptozotocin injection to induce DM or vehicle alone. Escalating doses of capsaicin (0.1–30 μM) or acetic acid (0.01–1%; AA) were perfused intraurethrally while recording isovolumetric bladder activity, urethral perfusion pressure, and electromyography of the external urethral sphincter (EUS-EMG). Some rats were additionally treated with α-bungarotoxin, hexamethonium, or bilateral transection of the sensory branches of the pudendal nerves (PudSNx). Intraurethral capsaicin inhibited bladder contractions in six out of seven control rats but not in any of six DM rats. Low-frequency oscillations (LFOs) of intraurethral pressure were observed in five out of six control rats with capsaicin-induced bladder inhibition. In contrast, intraurethral AA inhibited bladder contractions and enhanced tonic EUS-EMG activity in six out of six control and five out of six DM rats. LFOs occurred in four out of six control and three of five DM rats with AA-induced bladder inhibition. Chemically induced bladder inhibition and LFOs were not prevented by α-bungarotoxin but were eliminated by PudSNx and hexamethonium. Finally, LFOs were followed by phasic EUS activity. These findings show that DM affects urethral afferent neurons differentially, compromising those expressing TRPV1 receptors. Urethral smooth muscle LFOs are neurogenically mediated and induce EUS activity, revealing the existence of a hitherto undescribed reflex pathway: a smooth-to-striated muscle urethra-to-urethra reflex.


1992 ◽  
Vol 262 (4) ◽  
pp. H1149-H1155 ◽  
Author(s):  
K. C. Warnke ◽  
T. C. Skalak

To provide quantitative data on leukocyte plugging and to estimate its effects on blood flow resistance in the microcirculation, in vivo observations of leukocyte plugging of capillaries were made in all branches of 27 terminal arteriolar trees in spinotrapezius muscles of anesthetized Sprague-Dawley rats. The durations of 1,257 observed plugs had a lognormal distribution with a median of 0.12 s. Of 596 branches, 211 experienced at least one plug; this subpopulation had a median plugging frequency of 0.016/s and a median plugging fraction (plugging frequency times average duration) of 0.28%. A new variable, the network occlusion fraction, was defined to quantify plugging in a whole arteriolar tree. Applying in vivo data to a model relating plugging to resistance increases resulted in a lognormal distribution of resistance increases with a median of 1.6%. Each of the resistance increases that were greater than 3% was due to one or two individual leukocytes that plugged a capillary for greater than 30 s. The results suggest that, under physiological conditions, leukocyte plugging has little effect on blood flow resistance.


2008 ◽  
Vol 29 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Shuang Wang ◽  
Deng-chang Wu ◽  
Mei-ping Ding ◽  
Qing Li ◽  
Zhen-bing Zhuge ◽  
...  

Bioimpacts ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 219-226
Author(s):  
Zeinab Karimi ◽  
Sahar Janfeshan ◽  
Elias Kargar Abarghouei ◽  
Seyedeh-Sara Hashemi

Introduction: Acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) injury is a pro-inflammatory process that activates toll-like receptors (TLRs). Stem cell therapy holds a great promise for kidney repair. Therefore, we investigated the immunomodulatory role of bone marrow stromal cells (BMSCs) on TLR2 and TLR4 expression in AKI in male Sprague-Dawley rats. Methods: BMSCs were isolated from the bone marrow of male rats, cultured in DMEM, and characterized using appropriate markers before transplantation. Renal I/R was induced by 45 minutes bilateral ischemia followed by 24 hours of reperfusion. Rats received intraperitoneal injections of BMSCs (1.5 × 106 cells, i.p, per rat) immediately after termination of renal ischemia. Serum samples were collected pre-and post-stem cells injection for assessment of blood urea nitrogen (BUN) and creatinine (Cr) levels. The kidneys were harvested after 24 hours of reperfusion for structural and molecular analysis. Results: Renal I/R caused severe tissue injuries and increased the level of BUN (166.5 ± 12.9 vs. 18.25 ± 1.75) and Cr (3.7 ± 0.22 vs. 0.87 ± 0.06) compared to the sham group. In addition, mRNA expression of TLR2 and TLR4 elevated in the renal I/R group. Administration of BMSCs improved the functional and structural state of the kidney induced by I/R and down-regulated TLR2 and TLR4 gene expression. Conclusion: The results showed a highly significant renoprotection by BMSCs that indicates their therapeutic potential in I/R injures. These effects are most likely associated with the TLR2/4 signaling pathway via modulation of the inflammatory response cascades.


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