scholarly journals OPTOGENETICA: CONTROLLARE I NEURONI CON LA LUCE

2020 ◽  
Author(s):  
Anna Moroni
Keyword(s):  
Pain Relief ◽  
Blue Light ◽  
Neuronal Activity ◽  
Short Pulse ◽  
Cation Channels ◽  
K Channel ◽  
Neuronal Activation ◽  
Pain Model ◽  
Neuronal Inhibition

Optogenetics is a booming technique in neuroscience that allows manipualtion of neuronal activity by light. Neuronal activation can be achieved by the activation of light-gated cation channels while neuronal inhibition relies on the activation of chloride pumps and channels. We have engineered a light-gated potassium (K+) channel (BLINK) by linking the plant photoreceptor module LOV2 to the viral channel Kcv. Upon illumination with blue light (450 nm), BLINK channel hyperpolarizes neurons to EK and this effect persists for several minutes even in the dark. Pilot experiments in a mouse pain model show that this protracted light-off activity can be successfully employed for long term pain relief after activation of the channel by a short pulse of light.

Percutaneous glycerol rhizotomy for trigeminal neuralgia in patients with multiple sclerosis: a long-term retrospective cohort study

2020 ◽  
Vol 132 (5) ◽  
pp. 1405-1413 ◽  
Author(s):  
Michael D. Staudt ◽  
Holger Joswig ◽  
Gwynedd E. Pickett ◽  
Keith W. MacDougall ◽  
Andrew G. Parrent
Keyword(s):  
Multiple Sclerosis ◽  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Retrospective Chart Review ◽  
Medication Usage ◽  
Free Response ◽  
Free Survival ◽  
Time To Recurrence ◽  
Significant Difference

OBJECTIVEThe prevalence of trigeminal neuralgia (TN) in patients with multiple sclerosis (MS-TN) is higher than in the general population (idiopathic TN [ITN]). Glycerol rhizotomy (GR) is a percutaneous lesioning surgery commonly performed for the treatment of medically refractory TN. While treatment for acute pain relief is excellent, long-term pain relief is poorer. The object of this study was to assess the efficacy of percutaneous retrogasserian GR for the treatment of MS-TN versus ITN.METHODSA retrospective chart review was performed, identifying 219 patients who had undergone 401 GR procedures from 1983 to 2018 at a single academic institution. All patients were diagnosed with medically refractory MS-TN (182 procedures) or ITN (219 procedures). The primary outcome measures of interest were immediate pain relief and time to pain recurrence following initial and repeat GR procedures. Secondary outcomes included medication usage and presence of periprocedural hypesthesia.RESULTSThe initial pain-free response rate was similar between groups (p = 0.726): MS-TN initial GR 89.6%; MS-TN repeat GR 91.9%; ITN initial GR 89.6%; ITN repeat GR 87.0%. The median time to recurrence after initial GR was similar between MS-TN (2.7 ± 1.3 years) and ITN (2.1 ± 0.6 years) patients (p = 0.87). However, there was a statistically significant difference in the time to recurrence after repeat GR between MS-TN (2.3 ± 0.5 years) and ITN patients (1.2 ± 0.2 years; p < 0.05). The presence of periprocedural hypesthesia was highly predictive of pain-free survival (p < 0.01).CONCLUSIONSPatients with MS-TN achieve meaningful pain relief following GR, with an efficacy comparable to that following GR in patients with ITN. Initial and subsequent GR procedures are equally efficacious.

Temporal disconnection between pain relief and trigeminal nerve microstructural changes after Gamma Knife radiosurgery for trigeminal neuralgia

2020 ◽  
Vol 133 (3) ◽  
pp. 727-735
Author(s):  
Peter Shih-Ping Hung ◽  
Sarasa Tohyama ◽  
Jia Y. Zhang ◽  
Mojgan Hodaie
Keyword(s):  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Pain Intensity ◽  
Gamma Knife ◽  
Trigeminal Nerve ◽  
Diffusion Tensor ◽  
Gamma Knife Radiosurgery ◽  
Time Points ◽  
Microstructural Effect

OBJECTIVEGamma Knife radiosurgery (GKRS) is a noninvasive surgical treatment option for patients with medically refractive classic trigeminal neuralgia (TN). The long-term microstructural consequences of radiosurgery and their association with pain relief remain unclear. To better understand this topic, the authors used diffusion tensor imaging (DTI) to characterize the effects of GKRS on trigeminal nerve microstructure over multiple posttreatment time points.METHODSNinety-two sets of 3-T anatomical and diffusion-weighted MR images from 55 patients with TN treated by GKRS were divided within 6-, 12-, and 24-month posttreatment time points into responder and nonresponder subgroups (≥ 75% and < 75% reduction in posttreatment pain intensity, respectively). Within each subgroup, posttreatment pain intensity was then assessed against pretreatment levels and followed by DTI metric analyses, contrasting treated and contralateral control nerves to identify specific biomarkers of successful pain relief.RESULTSGKRS resulted in successful pain relief that was accompanied by asynchronous reductions in fractional anisotropy (FA), which maximized 24 months after treatment. While GKRS responders demonstrated significantly reduced FA within the radiosurgery target 12 and 24 months posttreatment (p < 0.05 and p < 0.01, respectively), nonresponders had statistically indistinguishable DTI metrics between nerve types at each time point.CONCLUSIONSUltimately, this study serves as the first step toward an improved understanding of the long-term microstructural effect of radiosurgery on TN. Given that FA reductions remained specific to responders and were absent in nonresponders up to 24 months posttreatment, FA changes have the potential of serving as temporally consistent biomarkers of optimal pain relief following radiosurgical treatment for classic TN.

Ultrasonic Percutaneous Tenotomy for Recalcitrant Lateral Elbow Tendinopathy: Clinical and Sonographic Results at 90 Months

2021 ◽  
pp. 036354652110101
Author(s):  
Benjamin F.H. Ang ◽  
P. Chandra Mohan ◽  
Meng Ai Png ◽  
John Carson Allen ◽  
Tet Sen Howe ◽  
...  
Keyword(s):  
Pain Relief ◽  
Extensor Tendon ◽  
Tissue Healing ◽  
Lateral Elbow ◽  
Percutaneous Tenotomy ◽  
Vas Scores ◽  
The Common ◽  
Lateral Elbow Tendinopathy

Background: In a study from our institution, ultrasonic percutaneous tenotomy of the brevis and the common extensor tendon for recalcitrant lateral elbow tendinopathy showed excellent safety profiles, high tolerability, efficiency, sustained pain relief, functional improvement, and sonographic evidence of tissue healing in 20 patients at 3 years’ follow-up. Purpose: To explore the long-term clinical and sonographic results of ultrasonic percutaneous tenotomy of the brevis and the common extensor tendon. Study Design: Case series; Level of evidence, 4. Methods: The same cohort of 20 patients was recalled after 7 years, and visual analog scale (VAS) for pain and Disabilities of the Arm, Shoulder and Hand (DASH) scores, need for secondary intervention, and overall satisfaction were assessed. They were also reassessed using ultrasound imaging of the brevis and the common extensor tendon to evaluate tendon hypervascularity, tendon thickness, and the progress or the recurrence of the hypoechoic scar tissue. Results: We successfully scored 19 patients and performed ultrasound on 16 patients with a median follow-up of 90 months (range, 86-102 months). There were no adverse outcomes and satisfaction remained at 100% (6 patients, satisfied; 13 patients, very satisfied). No patient developed a recurrence of symptoms and signs of lateral elbow tendinopathy, and therefore no secondary intervention was required. The improvement from baseline and early term scores was sustained ( P < .001 for all). At 90 months, there was a significant improvement in VAS scores and DASH–Compulsory scores compared with preprocedure scores and all follow-up times until 3 months. There was no difference in VAS scores and DASH–Compulsory scores at 90 months compared with 6 and 36 months. For DASH–Work scores, there was a significant improvement at 90 months compared with preprocedure scores, but there was no difference between DASH–Work scores at 90 months and scores at all other points of follow-up. At 90 months, hypervascularity remained resolved in 79% of patients, while all patients had reduced tendon swelling and sustained resolution or reduction of the hypoechoic lesion. Conclusion: At the long-term follow-up of 90 months, ultrasonic percutaneous tenotomy of the brevis and the common extensor tendon, previously shown to enhance recovery of lateral elbow tendinopathy, demonstrated good durability of pain relief and functional recovery that was previously achieved. This was accompanied by sustained sonographic tissue healing with no significant deterioration.

scholarly journals Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Mensch ◽  
Jade Dunot ◽  
Sandy M. Yishan ◽  
Samuel S. Harris ◽  
Aline Blistein ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strongly Correlated ◽  
App Processing ◽  
Term Potentiation ◽  
Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

scholarly journals The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy

2021 ◽  
Vol 22 (9) ◽  
pp. 4822
Author(s):  
Viktória Kovács ◽  
Gábor Remzső ◽  
Tímea Körmöczi ◽  
Róbert Berkecz ◽  
Valéria Tóth-Szűki ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Kynurenic Acid ◽  
Neuronal Damage ◽  
Brain Regions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Hippocampal Field ◽  
Power Spectral ◽  
Density Values ◽  
Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 ± 0.02, ΔBE = −17.6 ± 1.2 mmol/L, mean ± SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 °C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.

scholarly journals Memory-specific correlated neuronal activity in higher-order auditory regions of a parrot

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryohei Satoh ◽  
Hiroko Eda-Fujiwara ◽  
Aiko Watanabe ◽  
Yasuharu Okamoto ◽  
Takenori Miyamoto ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Higher Order ◽  
Auditory Memory ◽  
Neuronal Activation ◽  
Contact Calls ◽  
Contrast Exposure ◽  
Auditory Region ◽  
Neuronal Representation ◽  
Specific Association ◽  
Positive Correlations

AbstractMale budgerigars (Melopsittacus undulatus) are open-ended learners that can learn to produce new vocalisations as adults. We investigated neuronal activation in male budgerigars using the expression of the protein products of the immediate early genes zenk and c-fos in response to exposure to conspecific contact calls (CCs: that of the mate or an unfamiliar female) in three subregions (CMM, dNCM and vNCM) of the caudomedial pallium, a higher order auditory region. Significant positive correlations of Zenk expression were found between these subregions after exposure to mate CCs. In contrast, exposure to CCs of unfamiliar females produced no such correlations. These results suggest the presence of a CC-specific association among the subregions involved in auditory memory. The caudomedial pallium of the male budgerigar may have functional subdivisions that cooperate in the neuronal representation of auditory memory.

Outcome Predictors After Gamma Knife Radiosurgery for Recurrent Trigeminal Neuralgia

Neurosurgery ◽  
2010 ◽  
Vol 67 (6) ◽  
pp. 1637-1645 ◽  
Author(s):  
Hideyuki Kano ◽  
Douglas Kondziolka ◽  
Huai-Che Yang ◽  
Oscar Zorro ◽  
Javier Lobato-Polo ◽  
...  
Keyword(s):  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Gamma Knife ◽  
Pain Control ◽  
Surgical Procedure ◽  
Gamma Knife Radiosurgery ◽  
Sensory Loss ◽  
Failed Surgery ◽  
Gamma Knife Stereotactic Radiosurgery

Abstract BACKGROUND: Trigeminal neuralgia (TN) that recurs after surgery can be difficult to manage. OBJECTIVE: To define management outcomes in patients who underwent gamma knife stereotactic radiosurgery (GKSR) after failing 1 or more previous surgical procedures. METHODS: We retrospectively reviewed outcomes after GKSR in 193 patients with TN after failed surgery. The median patient age was 70 years (range, 26-93 years). Seventy-five patients had a single operation (microvascular decompression, n = 40; glycerol rhizotomy, n = 24; radiofrequency rhizotomy, n = 11). One hundred eighteen patients underwent multiple operations before GKSR. Patients were evaluated up to 14 years after GKSR. RESULTS: After GKSR, 85% of patients achieved pain relief or improvement (Barrow Neurological Institute grade I-IIIb). Pain recurrence was observed in 73 of 168 patients 6 to 144 months after GKSR (median, 6 years). Factors associated with better long-term pain relief included no relief from the surgical procedure preceding GKSR, pain in a single branch, typical TN, and a single previous failed surgical procedure. Eighteen patients (9.3%) developed new or increased trigeminal sensory dysfunction, and 1 developed deafferentation pain. Patients who developed sensory loss after GKSR had better long-term pain control (Barrow Neurological Institute grade I-IIIb: 86% at 5 years). CONCLUSION: GKSR proved to be safe and moderately effective in the management of TN that recurs after surgery. Development of sensory loss may predict better long-term pain control. The best candidates for GKSR were patients with recurrence after a single failed previous operation and those with typical TN in a single trigeminal nerve distribution.

Decreased neuronal inhibition in vitro after long-term administration of ethanol

Science ◽  
1984 ◽  
Vol 224 (4655) ◽  
pp. 1359-1361 ◽  
Author(s):  
D Durand ◽  
P. Carlen
Keyword(s):  
Neuronal Inhibition ◽  
Term Administration
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