General anesthesia plays a significant role in modern medicine. However, the precise mechanism of general anesthesia remains unclear, posing a key scientific challenge in anesthesiology. Advances in neuroscience techniques have enabled targeted manipulation of specific neural circuits and the capture of brain-wide neural activity at high resolution. These advances hold promise for elucidating the intricate mechanisms of action of general anesthetics. This review aims to summarize our current understanding of the role of cortical and subcortical nuclei in modulating general anesthesia, providing new evidence of cortico-cortical and thalamocortical networks in relation to anesthesia and consciousness. These insights contribute to a comprehensive understanding of the neural network mechanisms underlying general anesthesia.
Humans ; Anesthesia, General ; Animals ; Nerve Net/physiology* ; Cerebral Cortex/drug effects* ; Neural Pathways/drug effects* ; Thalamus/drug effects* ; Consciousness/drug effects*

Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP) is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV) metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD) patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug. The 64-year-old man with intractable CD experienced a sudden change in mental status, aphasia, and muscle weakness after IV administration of metronidazole. He had previously taken metronidazole orally for 13 years and received intermittent IV metronidazole treatments for CD exacerbation. Brain magnetic resonance imaging (MRI) showed high-intensity signals in the bilateral medial thalamus and the midbrain and pontine tegmentum on fluid-attenuated inversion recovery images. After discontinuation of metronidazole, the high-intensity brain MRI signals resolved and the patient's mental status dramatically improved; however, the patient exhibited mild cognitive dysfunction 2 months after the onset of encephalopathy.
Aphasia ; Bacterial Infections ; Brain ; Brain Diseases* ; Brain Diseases, Metabolic ; Crohn Disease* ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Magnetic Resonance Imaging ; Mesencephalon ; Metronidazole ; Middle Aged ; Muscle Weakness ; Pontine Tegmentum ; Thalamus

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.
Animals ; Benzothiazoles ; pharmacology ; Brain Chemistry ; drug effects ; Epilepsy ; chemically induced ; complications ; Hippocampus ; chemistry ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; Histidine ; pharmacology ; Hypothalamus ; chemistry ; Kindling, Neurologic ; physiology ; Memory Disorders ; drug therapy ; etiology ; Pentylenetetrazole ; Phenoxypropanolamines ; pharmacology ; Piperidines ; pharmacology ; Pyrilamine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H2 ; drug effects ; physiology ; Spatial Memory ; drug effects ; Spectrometry, Fluorescence ; Thalamus ; chemistry

OBJECTIVETo observe the protective effects of the Huanglian Jiedu decoction aqueous extract and its active fraction, which consists of total alkaloids, total flavonoids and total iridoid, on the thalamus of cerebral ischemia in rats.

METHODThe rat model of middle cerebral artery occlusion (MCAO) was chosen. Male SD rats were randomly divided into sham-operation group, model group, aqueous extract group (800 mg x kg(-1)), total alkaloids group(44 mg x kg(-1)), total flavonoids group (50 mg x kg(-1)) and the total iridoid group (80 mg x kg(-1)). The rats were administered the appropriate drugs intragastrically once a day, for 7 days after surgery. An equivalent volume of saline was given in the sham surgery and model groups. The HE staining was adopted to observe the pathological changes. Determination of Glu and gamma-GABA in thalamus were detected by HPLC with fluorescence detection. The expression of GAD65 was examined with immunohistochemistry and double staining with uorescent-conjugated antibodies against GFAP and Cx43 was chosen in this study.

RESULTThe neurons degenerated in MCAO rats after cerebral ischemia 7 d. The content of Glu, gamma-GABA decreased (P < 0.05), the expression of GAD65 reduced (P < 0.05) and the expression of GFAP and Cx43 increased (P < 0.01) in thalamus of rats compared with sham-operation group. Huanglian Jiedu decoction aqueous extract, total alkaloids, total flavonoids and total iridoid reduced the degeneration of neurons. Total flavonoids could promote the expression of GAD65 (P < 0.05) and decrease the expression of GFAP and Cx43 (P < 0.01) in thalamus compared with model group while it could also increased the content of Glu,gamma-GA BA to normal levels. Compared with model group, Huanglian Jiedu decoction aqueous extract, total alkaloids and total iridoid could raise the expression of Cx43, and Huanglian Jiedu decoction aqueous extract could also increase the expression of GAD65 (P < 0.05). The expression of GFAP in Huanglian Jiedu decoction aqueous extract group, total alkaloids group and total iridoid group were not different compared with model group while the content of gamma-GABA decreased (P < 0.05) compared with sham-operation group.

CONCLUSIONThe degeneration of nerve cells, the reduction of neurotransmitter amino acids content, the aberrant activation of astrocytes and the abnormal expression of GFAP and Cx43 will appear in thalamus of MCAO rats after ischemia. Huanglian Jiedu decoction total flavonoids could relieve the injury of nerve cell through inhibiting the abnormal activation of astrocytes and regulating the expression of GFAP and GAD65.

Animals ; Astrocytes ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Infarction, Middle Cerebral Artery ; drug therapy ; Male ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Thalamus ; drug effects

OBJECTIVETo investigate the expressions of gamma aminobutyric acid transporter 1 (GAT-1) and glutamate decarboxylase 65 (GAD65) mRNA in different brain regions at brain propofol uptake equilibrium in dogs.

METHODSEighteen 12- to 18-month-old healthy hybrid dogs were randomized equally into control group (group C), low dose group (group L), and high dose group (group H). In groups L and H, anesthesia was administered by intravenous injection of 5.5 and 7.0 mg/kg propofol followed by propofol infusion at a constant rate of 55 and 70 mg·kg(-1)·h(-1) for 50 min, respectively. Blood samples were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations, and the brain tissues of the hypothalamus, sub thalamus, dorsal thalamus, hippocampus, pons, parietal lobe and frontal lobe were examined for GAT-1 and GAD65 mRNA expressions using quantitative real-time PCR.

RESULTSIn groups L and H, propofol infusion at a constant rate for 50 min resulted in comparable plasma propofol concentrations between the internal carotid artery and jugular vein (P>0.05), but the concentrations differed significantly between the two groups (P<0.01). GAT-1 mRNA levels in the hypothalamus and hippocampus were significantly higher in groups L and H than in group C (P<0.05 and P<0.01), but comparable between the former two groups. The variations of GAT-1 mRNA levels between the hypothalamus and hippocampus were similar in both group L [(61.26∓7.17)% and (79.34∓39.95)%, P>0.05] and group H [(74.64∓19.63)% and (97.12∓32.31)%, P>0.05]. GAT-1 mRNA levels in other brain regions showed no significant difference among the 3 groups. GAD65 mRNA levels were similar between group L and group H, but both significantly higher than that in group C (P<0.01). GAD65 mRNA in other brain regions had no significant difference among the 3 groups.

CONCLUSIONGAT-1 mRNA in the hypothalamus and hippocampus and GAD65 mRNA in the dorsal thalamus are upregulated when propofol uptake reaches an equilibrium in the brain of dogs.

Animals ; Brain ; drug effects ; metabolism ; Dogs ; GABA Plasma Membrane Transport Proteins ; genetics ; metabolism ; Glutamate Decarboxylase ; genetics ; metabolism ; Hippocampus ; drug effects ; metabolism ; Hypothalamus ; drug effects ; metabolism ; Propofol ; pharmacology ; RNA, Messenger ; genetics ; Thalamus ; drug effects ; metabolism

OBJECTIVETo explore the effect of simulated navigation stimulation on the anesthetic sensitivity of sevoflurane in rats, so as to provide basis for rational using sevoflurane during navigation.

METHODSSD rats were stimulated by Crampton model and the conditioned taste aversion (CTA) was regarded as criterion of motion sickness. (1) 60 rats were randomly divided into control (n = 15) and rotation group (n = 45). The changes of behavior and autonomic activity, sevoflurane concentration achieved sleep and anesthesia states, and the revitalization time were observed in two group rats. (2) 32 rats were randomly divided into control (I), rotation (II), anesthesia (III) and rotation plus anesthesia (IV) group (n = 8). The acetylcholine (Ach), norepinephrine (NE), r-aminobutyric acid (GABA), glutamic acid (Glu) of brain cortex, thalamus and hippocampus were determined respectively in the four group rats.

RESULTSIn control group, the sevoflurane concentration achieved sleep and anesthesia states were 1.74% +/- 0.05% and 3.54% +/- 0.05% respectively, but, those concentrations were 1.51% +/- 0.06% and 3.14% +/- 0.08% in rotation group. There were lower significantly in rotation group than those in control group (P < 0.01). It was a major characteristic that all of the neurotransmitters were reduced significantly in II group, this was even more in brain cortex and thalamus (P < 0.01). In II group, Ach was upward in brain cortex, NE and GABA were reduced in hippocampus obviously. The change tendency of neurotransmitters in IV group was more close to II group, that was, the effect of rotation stimulation was more obvious.

CONCLUSIONThe anesthetic sensitivity of sevoflurane could be obvious increased in rats simulated navigation stimulation.

Anesthetics ; pharmacology ; Animals ; Cerebral Cortex ; drug effects ; metabolism ; Gravity, Altered ; Hippocampus ; drug effects ; metabolism ; Male ; Methyl Ethers ; pharmacology ; Neurotransmitter Agents ; analysis ; Norepinephrine ; analysis ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Rotation ; Thalamus ; drug effects ; metabolism ; gamma-Aminobutyric Acid ; analysis

Recent studies in western countries have reported that the mechanism pf pain are concorded with gate control opiage receptor binding sites and the release of intrinsic morphine like substances, sodium glutamate and also with bradykinin, seroconin, histamine and prostaglandin E. Otherwise the mechanism of the stimulstion producing analgesia has been reported to involve a neurophysiologic and neurohumoral inhibitory effect at the level of spinal cord, brain stem, thalamus and cortex. This has been clarified but further study should improve the chance of understanding the mechanism of pain. From the standpoint of pain management, medications used to manage pain have some unfortunate side effects. nerve blocks cause anesthesia toxicity, major neurosurgical procedures have many complications. Subarachnoidal and epidural analgesics have unknown irritation pneumonia and drug toxicity, and plexus or pituitary gland block with phenol or alcohol has uneventful complication. From January 1980 to December 1982, electrical acupuncture stimulation has been used on 210 cases at HANYANG university hospital in the pain clinic. I found it useful in relieving pain which has not responded to various conventional methods which included medications, nerve blocks, neurosurgical intervantion and neuropolytics. The results are as follows: 1) There are two kinds of treated patients: One is consultation case-12 from internal medicine, 16 from orthopedic surgery, 10 from neurosurgical and 2 from psychiatry. Another 170 cases were patients who directly to the clinic. And the age distribution shows the highset number of patients in the 3rd decade(21%) and in the 4th decade(24.8%). 2) The region of pain was 21% lumbar, 13.8% shoulder, 10% lower leg and head or face with 9.5%. 3) The duration of the pain showed 10 days 25.7%, 1~2 month 18.6%, one year 11.4% and the longest up to 20 years. 4) Patients who were able to walk into the clinic were 19.5%, moderate cases who to be accompanied were 58.6% and bedridden cases were 21.9%. 5) Treatment was conducted mainly on low frequency stimulation with various waves that included the general dynamic activity point plus reactive electro permeable point (REPP) 81.9% and REER plus head in situ needle 18.1%. 6) In 16.7% only one treatment was administered, in 46.1% 2~5 treatments were given, in 28.6% 6~10 treatments were given and in 3 cases more than 100 treatments were administered. 7) Of the 210 cases, 43.3% showed marked improvement, 41.4% were improved, 13.8% showed translent improvement and there were 3 cases of no improvement. The total confidence was 84.7%. 8) There are no serious complications except hypertensive shock case, submucosal hemorrhagic petechia 7 cases and generalized fatigue 18 cases. In conclusion, electrical acupuncture stimulation of the peripheral nervous system can be used to relieve pain replacing such conventional means as medications, nerve blocks, major neurosurgical procedures, neuroytics and physiopsychic therapy which are generally less effective.
Acupuncture ; Age Distribution ; Analgesia ; Analgesics ; Anesthesia ; Binding Sites ; Bradykinin ; Brain Stem ; Drug-Related Side Effects and Adverse Reactions ; Electric Stimulation* ; Fatigue ; Head ; Histamine ; Humans ; Internal Medicine ; Leg ; Morphine ; Needles ; Nerve Block ; Neurosurgical Procedures ; Orthopedics ; Pain Clinics ; Pain Management ; Peripheral Nerves* ; Peripheral Nervous System ; Phenol ; Pituitary Gland ; Pneumonia ; Shock ; Shoulder ; Sodium Glutamate ; Spinal Cord ; Thalamus