miR-181a expressed in the dorsal hippocampus regulates the reinstatement of cocaine CPP by targeting PRKAA1.

Neuroadaptive changes in the hippocampus underlie addictive-like behaviors in humans or animals chronically exposed to cocaine. miR-181a, which is widely expressed in the hippocampus, acts as a regulator for synaptic plasticity, while its role in drug reinstatement is unclear. In this study, we found that miR-181a regulates the reinstatement of cocaine conditioned place preference(CPP), and altered miR-181a expression changes the complexity of hippocampal neurons and the density and morphology of dendritic spines. By using a luciferase gene reporter, we found that miR-181a targets PRKAA1, an upstream molecule in the mTOR pathway. High miR-181a expression reduced the expression of the PRKAA1 mRNA and promoted mTOR activity and the reinstatement of cocaine CPP. These results indicate that miR-181a is involved in neuronal structural plasticity induced by reinstatement of cocaine CPP, possibly through the activation of the mTOR signaling pathway. This study provides new microRNA targets and a theoretical foundation for the prevention of cocaine-induced reinstatement.

A New Practical Method Based on MRI to Individually Localize the Transverse-Sigmoid Sinus Junction in Retrosigmoid Craniotomy: A Retrospective Before-After Study.

Background: Although the asterion has long been used as a skeletal surface marker of the transverse-sigmoid sinuses junction (TSSJ) point in the retrosigmoid approach, abundant evidence shows that the relationship between asterion and TSSJ point varies greatly. In recent years, new technologies have been developed, such as neuronavigation and three-dimensional volume rendering imaging, that can guide in exposing the TSSJ point individually. However, they are not only expensive but also difficult to apply in emergency surgery. Objective: To introduce a quick, practical, and low-cost new method for locating the TSSJ point precisely. Methods: In this retrospective before-after study, the test group located the TSSJ point with our new method during a 6-month period, while the control group used asterion as a surface landmark to estimate the TSSJ during the preceding 6 months. The primary outcome is the immediate exposure rate of the TSSJ point by the initial burr hole. Results: There were 60 patients in both control and test groups as no significant difference in the general clinical characteristics of both groups were observed. The new three-step method significantly increased the TSSJ exposure rate by initial burr hole compared with the control group (96.67% vs. 53.33%, P = 0.0002). Moreover, the total bone loss and craniotomy duration were significantly reduced by the new method. Incidence of sinus injury (10% vs. 6.6%), post-operation infection (3.33% vs. 3.33%), and CSF leakage (3.33% vs. 0%) were similar. Conclusions: The novel three-step approach accurately locates TSSJ points in retrosigmoid craniotomy, reduces bone defects, saves time, and does not increase the risk of sinus injury, infection, and CSF leakage.

Pre-operative external ventricle drainage improves neurological outcomes for patients with traumatic intracerebellar hematomas.

Objectives: Traumatic intracerebellar hematoma (TICH) is a very rare entity with a high morbidity and mortality rate, and there is no consensus on its optimal surgical management. In particular, whether and when to place external ventricle drainage in TICH patients without acute hydrocephalus pre-operation is still controversial. Methods: A single-institutional, retrospective analysis of total of 47 TICH patients with craniectomy hematoma evacuation in a tertiary medical center from January 2009 to October 2020 was performed. Primary outcomes were mortality in hospital and neurological function evaluated by GOS at discharge and 6 months after the ictus. Special attention was paid to the significance of external ventricular drainage (EVD) in TICH patients without acute hydrocephalus on admission. Results: Analysis of the clinical characteristics of the TICH patients revealed that the odds of use of EVD were seen in patients with IVH, fourth ventricle compression, and acute hydrocephalus. Placement of EVD at the bedside can significantly improve the GCS score before craniotomy, as well as the neurological score at discharge and 6 months. Compared with the only hematoma evacuation (HE) group, there is a trend that EVD can reduce hospital mortality and decrease the occurrence of delayed hydrocephalus, although the difference is not statistically significant. In addition, EVD can reduce the average NICU stay time, but has no effect on the total length of stay. Moreover, our data showed that EVD did not increase the risk of associated bleeding and intracranial infection. Interestingly, in terms of neurological function at discharge and 6 month after the ictus, even though without acute hydrocephalus on admission, the TICH patients can still benefit from EVD insertion. Conclusion: For TICH patients, perioperative EVD is safe and can significantly improve neurological prognosis. Especially for patients whose GCS dropped by more than 2 points before the operation, EVD can significantly improve the patient's GCS score, reduce the risk of herniation, and gain more time for surgical preparation. Even for TICH patients without acute hydrocephalus on admission CT scan, EVD placement still has positive clinical significance.

Association between Traumatic Subarachnoid Hemorrhage and Acute Respiratory Failure in Moderate-to-Severe Traumatic Brain Injury Patients.

Acute respiratory failure (ARF) with a high incidence among moderate-to-severe traumatic brain injury (M-STBI) patients plays a pivotal role in worsening neurological outcomes. Traumatic subarachnoid hemorrhage (tSAH) is highly prevalent in M-STBI, which is associated with significant adverse outcomes. In this retrospective cohort study, we aimed to explore the association between the severity of the tSAH and ARF in the M-STBI population. A total of 771 subjects were reviewed. Clinical and neuroimaging data of M-STBI patients were retrospectively collected, and ARF was ascertained retrospectively based on their electronic medical record. The degree of tSAH was classified according to Fisher's criteria, and the grade of tSAH was dichotomized to a low Fisher grade (Fisher grade 1-2) and a high Fisher grade (Fisher grade 3-4). After exclusion procedures, the data of 695 M-STBI patients were analyzed. A total of 284 (30.8%) had a high Fisher grade on admission. The overall rate of ARF within 48 h upon admission was 34.4% (239/695); it was 29.5% (142/481) and 46.3% (99/214) for the low and high Fisher groups, respectively. In a full cohort, a high Fisher grade was associated with ARF after adjusting for age, gender, GCS, smoking history, comorbidities, multiple injuries, characteristics of TBI, and pulmonary factors (OR 1.78; 95% CI, 1.11-2.85, p = 0.016). This result remained robust in the comparisons after PSM (71/132, 42.8% vs. 53/132, 31.9%; OR, 1.59; 95% CI, 1.02-2.49, p = 0.042). A high Fisher SAH grade exposure on admission is associated with ARF in M-STBI patients.

The optimized jugular vein catheterization reinforced cocaine self-administration addictive model for adult male Sprague-Dawley rats.

The self-administration (SA) model represents one of the most important and classic methods for drug addiction, and jugular vein catheterization is one of the most critical techniques in this animal model. We aimed to explore an optimized scheme to improve the success rate of rat jugular vein catheterization and SA model. Our experiment provided an optimized scheme which including numerous details, materials, approaches, updated techniques and protocols. Our experimental group consisted of 120 adult male Sprague-Dawley rats, which were divided into the Traditional Operation group (TO group) and the Optimized Operation group (OO group) by the random number table method and then further individually divided into the Saline Training group and the Cocaine Training group for the following SA training. Our results showed that the success rate of the jugular vein catheterization in the OO group was significantly greater than that in the TO group (93.33% vs 46.67%, χ2 = 31.11, P < 0.001). The optimized jugular vein catheterization could make the SA model more stable, reliable and efficient than the traditional operation. Compared with traditional methods, our optimized scheme made numerous improvements in materials and techniques including uniformity, individualized variability of the S-type positioning nail, the length and connection matching, the shape of the end and low cost. Our optimized scheme could provide a more stable and efficient tool for basic research on drug addiction. Several subtle improvements under our personal experience are usually important for augmenting operational efficiency.

Cerebral fat embolization with paroxysmal sympathetic hyperactivity syndrome and septic shock at high altitude: a case report and literature review.

BACKGROUND: Cerebral fat embolism (CFE) syndrome at high altitude was rare complicated with paroxysmal sympathetic hyperactivity (PSH) syndrome and septic shock. It is a challenge to differential diagnosis and treatment at high altitude. CASE PRESENTATION: This case presents a CFE with PSH and septic shock of a 23-year-old man occurred at high altitude of 3800 m above sea level, transferred by airplane successfully and cured in the department of neurosurgery, Xi'an Tangdu Hospital. CONCLUSIONS: It is key that CFE with PSH can be rapid diagnosed and treatment bundles of septic shock should be initiated as soon as possible. Early neurological rehabilitation played an important role for good outcome.

Effects of Primary Decompressive Craniectomy on the Outcomes of Serious Traumatic Brain Injury with Mass Lesions, and Independent Predictors of Operation Decision.

BACKGROUND: Although operative indications for traumatic brain injury (TBI) are known, neurosurgeons are unsure whether to remove the bone flap after mass lesion extraction, and an efficient scoring system for predicting which patients should undergo decompressive craniectomy (DC) does not exist. METHODS: Nine parameters were assessed. In total, 245 patients with severe TBI were retrospectively assessed from June 2015 to May 2019, who underwent DC or craniotomy to remove mass lesions. The 6-month mortality and Extended Glasgow Outcome Scale scores were compared between the DC and craniotomy groups. Using univariable and multivariable logistic regression equations, receiver operating characteristic curves were obtained for predicting the decision for DC. RESULTS: The overall 6-month mortality in the entire cohort was 11.43% (28/245). Patients undergoing DC had lower mean preoperative Glasgow Coma Scale scores (P = 0.01), and higher amounts of individuals with a Glasgow Coma Scale score of 6 (P = 0.007), unresponsive pupillary light reflex (P < 0.001), closed basal cisterns (P < 0.001), and diffuse injury (P = 0.025), compared with the craniotomy group. Because of high disease severity, individuals administered primary DC showed increased 6-month mortality compared with the craniotomy group. However, in surviving patients, favorable Extended Glasgow Outcome Scale rates were similar in both groups. Pupillary light reflex and basal cisterns were independent predictors of the DC decision. Based on receiver operating characteristic curves, the model had sensitivity and specificity of 81.6% and 84.9%, respectively, in predicting the probability of DC. CONCLUSIONS: These preliminary data showed that primary DC may benefit some patients with severe TBI with mass lesions. In addition, unresponsive preoperative pupil reaction and closed basal cistern could predict the DC decision.

Coexpression of VGLUT1 and VGLUT2 in precerebellar neurons in the lateral reticular nucleus of the rat.

Vesicular glutamate transporter (VGLUT) 1 and VGLUT2 have been reported to distribute complementally in most brain regions and have been assumed to define distinct functional elements. Previous studies have shown the expression of VGLUT1 mRNA and VGLUT2 mRNA in the lateral reticular nucleus (LRN), a key precerebellar nucleus sending mossy fibers to the cerebellum. In the present study, we firstly examined the coexpression of VGLUT1 and VGLUT2 mRNA in the LRN of the rat by dual-fluorescence in situ hybridization. About 81.89 % of glutamatergic LRN neurons coexpressed VGLUT1 and VGLUT2 mRNA, and the others expressed either VGLUT1 or VGLUT2 mRNA. We then injected the retrograde tracer Fluogold (FG) into the vermal cortex of cerebellum, and observed that 95.01 % and 86.80 % of FG-labeled LRN neurons expressed VGLUT1 or VGLUT2 mRNA respectively. We further injected the anterograde tracer biotinylated dextran amine (BDA) into the LRN, and found about 82.6 % of BDA labeled axon terminals in the granular layer of cerebellar cortex showed both VGLUT1- and VGLUT2-immunoreactivities. Afterwards, we observed under electron microscopy that anterogradely labeled axon terminals showing immunoreactivity for VGLUT1 or VGLUT2 made asymmetric synapses with dendritic profiles of cerebellar neurons. Finally, we selectively down-regulated the expression of VGLUT1 mRNA or VGLUT2 mRNA by using viral vector mediated siRNA transfection and detected that the fine movements of the forelimb of rats were disturbed. These results indicated that LRN neurons coexpressing VGLUT1 and VGLUT2 project to the cerebellar cortex and these neurons might be critical in mediating the forelimb movements.

The NAc lesions disrupted the hippocampus-mPFC theta coherence during intravenous cocaine administration in rats.

Synchronization and desynchronization of neuronal oscillatory activities between different brain areas play an important role in effective information communication. The hippocampus-mPFC circuit is well recognized as an important neural circuit pathway involved in drug addiction. We aimed to examine cocaine-related changes in oscillation synchronization in the hippocampus-mPFC circuit and to explore the role of the NAc in oscillation synchronization between the hippocampus and the mPFC during intravenous cocaine administration. In our experiment, adult male Sprague-Dawley rats were divided into the Saline group, Cocaine group and Lesion group by the random number table method. Using an electrophysiological method, we continuously recorded the local field potentials (LFPs) of the hippocampus and the mPFC after pulse intravenous cocaine or saline. Our results showed that theta coherence occurred in the hippocampus-mPFC circuit during intravenous cocaine administration (Coherenceθ, Pre-drug = 0.2212 ±â€¯0.0126, Coherenceθ, Post-drug = 0.3118 ±â€¯0.0149, t = 4.894, P < 0.001), and the NAc Lesions could disrupt hippocampus-mPFC theta coherence (Coherenceθ, Pre-drug = 0.3164 ±â€¯0.0188, Coherenceθ, Post-drug = 0.2628 ±â€¯0.0248, t = 2.408, P < 0.05). These findings indicated that the NAc could influence oscillation synchronization between the hippocampus and mPFC during intravenous cocaine administration, which might help to elucidate the neurophysiological mechanisms of the neural circuits that underlie the function of the NAc during the strengthening of drug addiction.

Altered Activity of SK Channel Underpins Morphine Withdrawal Relevant Psychiatric Deficiency in Infralimbic to Accumbens Shell Pathway.

Drug addiction can be viewed as a chronic psychiatric disorder that is related to dysfunction of neural circuits, including reward deficits, stress surfeits, craving changes, and compromised executive function. The nucleus accumbens (NAc) plays a crucial role in regulating craving and relapse, while the medial prefrontal cortex (mPFC) represents a higher cortex projecting into the NAc that is active in the management of executive function. In this study, we investigated the role of the small conductance calcium-activated potassium channels (SK channels) in NAc and mPFC after morphine withdrawal. Action potential (AP) firing of neurons in the NAc shell was enhanced via the downregulations of the SK channels after morphine withdrawal. Furthermore, the expression of SK2 and SK3 subunits in the NAc was significantly reduced after 3 weeks of morphine withdrawal, but was not altered in the dorsal striatum. In mPFC, the SK channel subunits were differentially expressed. To be specific, the expression of SK3 was upregulated, while the expression of SK2 was unchanged. Furthermore, the AP firing in layer 5 pyramidal neurons of the infralimbic (IL) cortex was decreased via the upregulations of the SK channel-related tail current after 3 weeks of morphine withdrawal. These results suggest that the SK channel plays a specific role in reward circuits following morphine exposure and a period of drug withdrawal, making it a potential target for the prevention of relapse.

Vesicular glutamate transporter isoforms: The essential players in the somatosensory systems.

In nervous system, glutamate transmission is crucial for centripetal conveyance and cortical perception of sensory signals of different modalities, which necessitates vesicular glutamate transporters 1-3 (VGLUT 1-3), the three homologous membrane-bound protein isoforms, to load glutamate into the presysnaptic vesicles. These VGLUTs, especially VGLUT1 and VGLUT2, selectively label and define functionally distinct neuronal subpopulations at each relay level of the neural hierarchies comprising spinal and trigeminal sensory systems. In this review, by scrutinizing each structure of the organism's fundamental hierarchies including dorsal root/trigeminal ganglia, spinal dorsal horn/trigeminal sensory nuclear complex, somatosensory thalamic nuclei and primary somatosensory cortex, we summarize and characterize in detail within each relay the neuronal clusters expressing distinct VGLUT protein/transcript isoforms, with respect to their regional distribution features (complementary distribution in some structures), axonal terminations/peripheral innervations and physiological functions. Equally important, the distribution pattern and characteristics of VGLUT1/VGLUT2 axon terminals within these structures are also epitomized. Finally, the correlation of a particular VGLUT isoform and its physiological role, disclosed thus far largely via studying the peripheral receptors, is generalized by referring to reports on global and conditioned VGLUT-knockout mice. Also, researches on VGLUTs relating to future direction are tentatively proposed, such as unveiling the elusive differences between distinct VGLUTs in mechanism and/or pharmacokinetics at ionic/molecular level, and developing VGLUT-based pain killers.

Neurokinin-1 Receptor-Immunopositive Neurons in the Medullary Dorsal Horn Provide Collateral Axons to both the Thalamus and Parabrachial Nucleus in Rats.

It has been suggested that the trigemino-thalamic and trigemino-parabrachial projection neurons in the medullary dorsal horn (MDH) are highly implicated in the sensory-discriminative and emotional/affective aspects of orofacial pain, respectively. In previous studies, some neurons were reported to send projections to both the thalamus and parabrachial nucleus by way of collaterals in the MDH. However, little is known about the chemoarchitecture of this group of neurons. Thus, in the present study, we determined whether the neurokinin-1 (NK-1) receptor, which is crucial for primary orofacial pain signaling, was expressed in MDH neurons co-innervating the thalamus and parabrachial nucleus. Vesicular glutamate transporter 2 (VGLUT2) mRNA, a biomarker for the subgroup of glutamatergic neurons closely related to pain sensation, was assessed in trigemino-parabrachial projection neurons in the MDH. After stereotactic injection of fluorogold (FG) and cholera toxin subunit B (CTB) into the ventral posteromedial thalamic nucleus (VPM) and parabrachial nucleus (PBN), respectively, triple labeling with fluorescence dyes for FG, CTB and NK-1 receptor (NK-1R) revealed that approximately 76 % of the total FG/CTB dually labeled neurons were detected as NK-1R-immunopositive, and more than 94 % of the triple-labeled neurons were distributed in lamina I. In addition, by FG retrograde tract-tracing combined with fluorescence in situ hybridization (FISH) for VGLUT2 mRNA, 54, 48 and 70 % of FG-labeled neurons in laminae I, II and III, respectively, of the MDH co-expressed FG and VGLUT2 mRNA. Thus, most of the MDH neurons co-innervating the thalamus and PBN were glutamatergic. Most MDH neurons providing the collateral axons to both the thalamus and parabrachial nucleus in rats were NK-1R-immunopositive and expressed VGLUT2 mRNA. NK-1R and VGLUT2 in MDH neurons may be involved in both sensory-discriminative and emotional/affective aspects of orofacial pain processing.

Decreased HCN2 expression in STN contributes to abnormal high-voltage spindles in the cortex and globus pallidus of freely moving rats.

Abnormal oscillation in the cortical-basal ganglia loop is involved in the pathophysiology of parkinsonism. High-voltage spindles (HVSs), one of the main type abnormal oscillations in Parkinson's disease, are regulated by dopamine D2-like receptors but not D1-like receptors. However, little is known about how dopamine D2-like receptors regulate HVSs and the role of hyperpolarization-activated cyclic nucleotide-gated2 (HCN2) in HVSs regulation. We simultaneously recorded the local field potential (LFP) in globus pallidus (GP) and electrocorticogram (ECoG) in primary motor cortex (M1) in freely moving 6-hydroxydopamine (6-OHDA) lesioned or control rats. The expression of HCN2 and dopamine D2 receptor in the subthalamic nucleus (STN) was examined by immunochemical staining and Western blotting. We also tested the role of HCN2 in HVSs regulation by using pharmacological and shRNA methodology. We found that dopamine D2-like receptor agonists suppressed the increased HVSs in 6-OHDA lesioned rats. HCN2 was co-expressed with dopamine D2 receptor in the STN, and dopamine depletion decreased the expression of HCN2 as well as dopamine D2 receptor which contribute to the regulation of HVSs. HCN2 was down regulated by HCN2 shRNA, which thereby led to an increase in the HVSs in naïve rats while HCN2 agonist reduced the HVSs in 6-OHDA lesioned rats. These results suggest that HCN2 in the STN is involved in abnormal oscillation regulation between M1 cortex and GP.

High frequency stimulation of the STN restored the abnormal high-voltage spindles in the cortex and the globus pallidus of 6-OHDA lesioned rats.

Many studies showed that abnormal oscillations in the cortical-basal ganglia loop is involved in the pathophysiology of Parkinson's disease (PD). In contrast to the well-studied beta synchronization, high-voltage spindles (HVSs), another type of abnormal oscillation observed in PD, are neglected. To explore the role of subthalamic nucleus-deep brain stimulation (STN-DBS) in HVSs regulation, we simultaneously recorded the local field potential (LFP) in the globus pallidus (GP) and electrocorticogram (ECoG) in the primary motor cortex(M1) in freely moving 6-hydroxydopamine (6-OHDA) lesioned or control rats before, during, and after STN-DBS. Consistent with our previous study, HVSs occurrence, duration, and relative power and coherence between the M1 cortex and GP increased in 6-OHDA lesioned rats. We found that high but not low frequency stimulation restored the abnormal HVSs activity and motor deficit. These results suggest that the STN is involved in the abnormal oscillation between the M1 cortex and GP.

Long-Term Changes in Drug Craving and Nutritional Status of Opioid Addicts with Nucleus Accumbens Ablative Stereotactic Neurosurgery at Five Years Postoperatively.

BACKGROUND: The nucleus accumbens (NAcc) has been proven to be associated with drug and food craving. NAcc ablative neurosurgery has been suggested to modulate the balance of the brain reward system and thus alleviate drug dependence in patients. It has been hypothesized that it would also alleviate food craving in patients as well as altering their nutritional status. AIMS: This study aimed to estimate the effect of NAcc neurosurgery on drug craving and nutritional status in patients with drug dependence at 5 years postoperatively. METHODS: The study included 100 patients with NAcc surgery and 92 patients without surgery. Body mass index (BMI) and body fat percentage (BF%) were examined to assess nutritional status, and questionnaires were administered to assess drug craving. RESULTS: Compared with the nonsurgery group and the relapse patients from the surgery group, the nonrelapse patients from the surgery group had higher BMI and BF% but lower drug craving. There were no significant differences between the nonsurgery group and the relapse patients in BMI, but the relapse patients had higher drug craving than the nonsurgery group. CONCLUSIONS: Long-term follow-up suggested that NAcc ablative neurosurgery would alleviate drug craving and yield a better nutritional status if individuals sustained abstinence. It would increase drug craving but would not ruin the nutritional status of patients even when individuals relapsed postoperatively.

Differential expression of VGLUT1 or VGLUT2 in the trigeminothalamic or trigeminocerebellar projection neurons in the rat.

The vesicular glutamate transporters, VGLUT1 and VGLUT2, reportedly display complementary distribution in the rat brain. However, co-expression of them in single neurons has been reported in some brain areas. We previously found co-expression of VGLUT1 and VGLUT2 mRNAs in a number of single neurons in the principal sensory trigeminal nucleus (Vp) of the adult rat; the majority of these neurons sent their axons to the thalamic regions around the posteromedial ventral nucleus (VPM) and the posterior nuclei (Po). It is well known that trigeminothalamic (T-T) projection fibers arise not only from the Vp but also from the spinal trigeminal nucleus (Vsp), and that trigeminocerebellar (T-C) projection fibers take their origins from both of the Vp and Vsp. Thus, in the present study, we examined the expression of VGLUT1 and VGLUT2 in Vp and Vsp neurons that sent their axons to the VPM/Po regions or the cortical regions of the cerebellum. For this purpose, we combined fluorescence in situ hybridization (FISH) histochemistry with retrograde tract-tracing; immunofluorescence histochemistry was also combined with anterograde tract-tracing. The results indicate that glutamatergic Vsp neurons sending their axons to the cerebellar cortical regions mainly express VGLUT1, whereas glutamatergic Vsp neurons sending their axons to the thalamic regions express VGLUT2. The present data, in combination with those of our previous study, indicate that glutamatergic Vp neurons projecting to the cerebellar cortical regions express mainly VGLUT1, whereas the majority of glutamatergic Vp neurons projecting to the thalamus co-express VGLUT1 and VGLUT2.

Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

High-voltage spindles (HVSs) have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP) and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D1-like receptors or D2-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1) in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D2-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D2-like receptor antagonists. On the contrary, the selective dopamine D1-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D2-like receptors, but not D1-like receptors, were involved in HVS regulation. This supports the important role of dopamine D2-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

Nucleus accumbens surgery for addiction.

BACKGROUND: Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery because of psychological dependence. Multiple studies identify a central role of the nucleus accumbens (NAc) in addiction; several studies note decreased addictive behavior after interventions in this area. METHODS: Based on animal experiments, our institute started the clinical trial for the treatment of drug addicts' psychological dependence by making lesions in the bilateral NAc with stereotactic surgery from July 2000. RESULTS: The short-term outcomes were encouraging and triggered rapid application of this treatment in China from 2003 to 2004. However, lack of long-term outcomes and controversy eventually led to halting the surgery for addiction by the Ministry of Health of China in November 2004 and a nationwide survey about it later. Our institute had performed this surgery in 272 patients with severe heroin addiction. The follow-up study showed that the 5-year nonrelapse rate was 58% and the quality of life was significantly improved. Patients had several kinds of side effects, but the incidence rate was relatively low. The patients gradually recovered more than 5 years after the surgery. The side effects did not severely influence an individual's life or work. Nationwide surgery showed that the nonrelapse rate was 50% in the sample of 150 cases, from 1167 patients overall who underwent stereotactic surgery in China. CONCLUSIONS: Although sometimes accompanied by neuropsychological adverse events, stereotactic ablation of NAc may effectively treat opiate addiction. Lesion location has a significant impact on treatment efficacy and requires further study. Because ablation is irreversible, the NAc surgery for addiction should be performed with cautiousness, and deep brain stimulation (DBS) is an ideal alternative.

Deep brain stimulation of the bilateral nucleus accumbens in normal rhesus monkey.

The nucleus accumbens (NAc) has been considered as a novel target of deep brain stimulation (DBS) for intractable psychiatric disorders. Quite a few questions exist about this new treatment, and might be explored in nonhuman primate models. There are several reports on DBS of brain nucleus other than NAc in nonhuman primates. Therefore, we stereotactically implanted the electrodes into bilateral NAc under the guidance of MRI using a clinical Leksell stereotactic system in normal rhesus monkeys. NAc could be recognized as the area of continuity between the caudate nucleus and putamen in the coronal sections, which is beneath the internal capsule, and the gray matter nucleus between the ventromedial prefrontal cortex and anterior commissure in axial sections, which is medial to the putamen. NAc is mainly at a point 2.0-3.0 mm inferior, 3.0-4.0 mm anterior, and 4.5-5.5 mm lateral to the anterior commissure. The electrodes were implanted accurately and connected to an implantable pulse generator subcutaneously. After recovery from surgery, stimulation with a variety of parameters was trialed, and continuous stimulation at 90 µs, 3.5 V, 160, or 60 Hz was administered individually for 7 days. The behaviors and spontaneous locomotor activity of the animals did not change significantly during stimulation. This is the first report on DBS of NAc in nonhuman primates to the best of our knowledge. Bilateral electrical stimulation of NAc is a safe treatment. This model could be helpful in further studies on the clinical use of NAc stimulation for psychiatric disorders and for a better understanding of the functions of this nucleus.

The Inhibition of Spinal Astrocytic JAK2-STAT3 Pathway Activation Correlates with the Analgesic Effects of Triptolide in the Rat Neuropathic Pain Model.

Neuropathic pain (NP) is an intractable clinical problem without satisfactory treatments. However, certain natural products have been revealed as effective therapeutic agents for the management of pain states. In this study, we used the spinal nerve ligation (SNL) pain model to investigate the antinociceptive effect of triptolide (T10), a major active component of the traditional Chinese herb Tripterygium wilfordii Hook F. Intrathecal T10 inhibited the mechanical nociceptive response induced by SNL without interfering with motor performance. Additionally, the anti-nociceptive effect of T10 was associated with the inhibition of the activation of spinal astrocytes. Furthermore, intrathecal administration of T10 attenuated SNL-induced janus kinase (JAK) signal transducers and activators of transcription 3 (STAT3) signalling pathway activation and inhibited the upregulation of proinflammatory cytokines, such as interleukin-6, interleukin-1 beta, and tumour necrosis factor-α, in dorsal horn astrocytes. Moreover, NR2B-containing spinal N-methyl D-aspartate receptor (NMDAR) was subsequently inhibited. Above all, T10 can alleviate SNL-induced NP via inhibiting the neuroinflammation in the spinal dorsal horn. The anti-inflammation effect of T10 may be related with the suppression of spinal astrocytic JAK-STAT3 activation. Our results suggest that T10 may be a promising drug for the treatment of NP.