OBJECTIVES: To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death. METHODS: PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis. RESULTS: Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine). CONCLUSIONS GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.
Rats ; Animals ; Metabolomics/methods* ; Brain Injuries ; Biomarkers/metabolism* ; Brain Stem/metabolism*

A triple-transgenic (tyrosine hydroxylase/dopamine decarboxylase/GTP cyclohydrolase 1, TH/DDC/GCH1) bone marrow mesenchymal stem cell line (BMSCs) capable of stably synthesizing dopamine (DA) transmitters were established to provide experimental evidence for the clinical treatment of Parkinson's disease (PD) by using this cell line. The DA-BMSCs cell line that could stably synthesize and secrete DA transmitters was established by using the triple transgenic recombinant lentivirus. The triple transgenes (TH/DDC/GCH1) expression in DA-BMSCs was detected using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Moreover, the secretion of DA was tested by enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Chromosome G-banding analysis was used to detect the genetic stability of DA-BMSCs. Subsequently, the DA-BMSCs were stereotactically transplanted into the right medial forebrain bundle (MFB) of Parkinson's rat models to detect their survival and differentiation in the intracerebral microenvironment of PD rats. Apomorphine (APO)-induced rotation test was used to detect the improvement of motor dysfunction in PD rat models with cell transplantation. The TH, DDC and GCH1 were expressed stably and efficiently in the DA-BMSCs cell line, but not expressed in the normal rat BMSCs. The concentration of DA in the cell culture supernatant of the triple transgenic group (DA-BMSCs) and the LV-TH group was extremely significantly higher than that of the standard BMSCs control group (P < 0.000 1). After passage, DA-BMSCs stably produced DA. Karyotype G-banding analysis showed that the vast majority of DA-BMSCs maintained normal diploid karyotypes (94.5%). Moreover, after 4 weeks of transplantation into the brain of PD rats, DA-BMSCs significantly improved the movement disorder of PD rat models, survived in a large amount in the brain microenvironment, differentiated into TH-positive and GFAP-positive cells, and upregulated the DA level in the injured area of the brain. The triple-transgenic DA-BMSCs cell line that stably produced DA, survived in large numbers, and differentiated in the rat brain was successfully established, laying a foundation for the treatment of PD using engineered culture and transplantation of DA-BMSCs.
Rats ; Animals ; Dopamine ; Parkinson Disease/metabolism* ; Mesenchymal Stem Cells/metabolism* ; Cell Line ; Brain/metabolism* ; Cell Differentiation ; Mesenchymal Stem Cell Transplantation

Glioma is the most common and lethal intrinsic primary tumor of the brain. Its controversial origins may contribute to its heterogeneity, creating challenges and difficulties in the development of therapies. Among the components constituting tumors, glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation. Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor, in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation. Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states, glial, neural, and immune cell populations in the tumor microenvironment. Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy. Here, we discuss the heterogeneity and relevant functions of tumor cell state, microglia, monocyte-derived macrophages, and neurons in glioma, highlighting their bilateral effects on tumors. Finally, we describe potential therapeutic approaches and targets beyond standard treatments.
Humans ; Glioma/metabolism* ; Neuroglia/metabolism* ; Carcinogenesis/pathology* ; Neural Stem Cells/metabolism* ; Microglia/metabolism* ; Brain Neoplasms/metabolism* ; Tumor Microenvironment

In healthy individuals, energy intake is in balance with energy expenditure, which helps to maintain a normal body weight. The brain's inability to control energy homeostasis underlies the pathology of hyperphagia and obesity. The brain detects body energy excess and deficit by sensing the levels of circulating metabolic hormones and nutrients and by receiving metabolic information from the periphery via the autonomic nervous system. A specialized neuronal network coordinates energy intake behavior and the metabolic processes affecting energy expenditure. Here, we briefly review neuronal mechanisms by which our body maintains energy balance.
Autonomic Nervous System ; Brain Stem ; Brain* ; Energy Intake ; Energy Metabolism* ; Homeostasis ; Hyperphagia ; Hypothalamus ; Ideal Body Weight ; Metabolism ; Neurons ; Obesity ; Pathology

OBJECTIVETo study the effect of nitric oxide (NO) in vestibular compensation after unilateral vestibular deafferentation.

METHODSEighteen animals were divided into two groups, 6 of group a as control, 12 of group b received gentamicin intratympanic injection in the left ear. Half of the animals were killed respectively after 5 days and 10 days. Vestibular endorgan and brainstem tissue sections were subjected to NADPH-d reactive test of NOS for histochemical examination.

RESULTSIn group a, NOS-like reactivity in both sides of vestibular endorgan and nucli. In group b during 5 days, NOS-like reactivity in right side of vestibular endorgan and nucli, those of the left side were negative. During 10 days, NOS-like reactivity only in the right side of vestibular endorgan.

CONCLUSIONSChanges of NOS expression in the contralateral vestibular nucli might have played a role in vestibular compensation.

Adaptation, Physiological ; Animals ; Brain Stem ; metabolism ; physiopathology ; Evoked Potentials, Auditory, Brain Stem ; Female ; Gentamicins ; Guinea Pigs ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Vestibular Nerve ; metabolism ; Vestibular Nuclei ; metabolism ; physiopathology ; Vestibule, Labyrinth ; injuries ; metabolism ; physiopathology

Traumatic brain injury (TBI) contributes to the key causative elements of neurological deficits. However, no effective therapeutics have been developed yet. In our previous work, extracellular vesicles (EVs) secreted by stem cells from human exfoliated deciduous teeth (SHED) offered new insights as potential strategies for functional recovery of TBI. The current study aims to elucidate the mechanism of action, providing novel therapeutic targets for future clinical interventions. With the miRNA array performed and Real-time PCR validated, we revealed the crucial function of miR-330-5p transferred by SHED-derived EVs (SHED-EVs) in regulating microglia, the critical immune modulator in central nervous system. MiR-330-5p targeted Ehmt2 and mediated the transcription of CXCL14 to promote M2 microglia polarization and inhibit M1 polarization. Identified in our in vivo data, SHED-EVs and their effector miR-330-5p alleviated the secretion of inflammatory cytokines and resumed the motor functional recovery of TBI rats. In summary, by transferring miR-330-5p, SHED-EVs favored anti-inflammatory microglia polarization through Ehmt2 mediated CXCL14 transcription in treating traumatic brain injury.
Animals ; Brain Injuries, Traumatic/therapy* ; Chemokines, CXC/metabolism* ; Extracellular Vesicles/metabolism* ; Histocompatibility Antigens/metabolism* ; Histone-Lysine N-Methyltransferase/metabolism* ; Humans ; MicroRNAs/metabolism* ; Microglia/metabolism* ; Rats ; Stem Cells/metabolism*

AIMTo investigate the change of NMDAR1 (zeta 1) subunit expression in temple cortex, frontal lobe, hippocampus and cerebellum of three different group rat after 98 dB wide frequency noise exposure.

METHODSWestern Blot and RT-PCR technique, combined with auditory brainstem response (ABR) measurement.

RESULTS(1) Expressions of NMDAR1 (zeta 1) subunit in frontal cortex, temple cortex, hippocampus and cerebellum have no difference, but AD model rat is much weaker than the control group. (2) Expression of NMDAR2A (epsilon 1) in temple cortex for physiological saline groups rat have a mostly increase (plus noise), moreover, those are weakest expression in hippocampus. NMDAR1 (zeta 1) subunit in cerebellum have highest expression, moreover, it is weakest in temple cortex. (3) NMDAR1 (zeta1), NMDAR2A (epsilon 1) subunit expression in hippocampus for three groups rat have a down-regulation after adding noise. (4) NMDAR1 (zeta 1), NMDAR2A (epsilon 1) subunit mRNA expression in control group have no remarkable difference in different cortex. (5) Expressions of NMDAR2A (epsilon 1) in frontal temple cortex, hippocampus for AD model rat are less than that of other groups, weakest in cerebellum, weaker in frontal.

CONCLUSIONWide band frequency noise can reduce the expression of NMDAR1 (zeta 1) subunit in hippocampus and cerebellum of AD model rat, however, the way of regulation is not in the mRNA level. Wide band frequency noise can inhibit the expression of NMDAR2A (epsilon 1) in hippocampus, temple cortex of AD model rat, which has been regulated by mRNA level and have cortex area difference.

Animals ; Brain ; metabolism ; Cerebral Cortex ; metabolism ; Evoked Potentials, Auditory, Brain Stem ; Glutamic Acid ; poisoning ; Noise ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism

OBJECTIVE: To study the effect of primary brain-stem injury on the expression of basic fibroblast growth factor (bFGF) in the reticular formation of medulla oblongata. METHODS: Immunohistochemical SABC was used to study the change of bFGF expression in the reticular formation of medulla oblongata after brain-stem injury by striking. RESULTS: The numbers of positive cells and positive intensity of the study group in the reticular formation of medulla oblongata were significantly elevated than those of the control group and the postmortem injury group. CONCLUSION The expression of bFGF is elevated in reticular formation after brain-stem injury.
Animals ; Brain Stem/injuries* ; Female ; Fibroblast Growth Factor 2/biosynthesis* ; Male ; Medulla Oblongata/metabolism* ; Rats ; Rats, Wistar ; Reticular Formation/metabolism*

Animals ; Brain Neoplasms ; etiology ; metabolism ; pathology ; Glioma ; etiology ; metabolism ; pathology ; Humans ; Neoplastic Stem Cells ; pathology ; physiology ; Signal Transduction ; Stem Cell Research

OBJECTIVETo investigate the effect of noise on the antioxidant capacity in different regions of brain tissue in guinea pigs.

METHODSThirty male white red-eye guinea pigs were equally and randomly divided into five groups: 1-, 3-, 7-, and 14-day groups after noise exposure and control group. The guinea pigs of the experimental groups were exposed to steady white noise with a sound pressure level at 100 dB for 8 h per day and for 2 consecutive days. The auditory brainstem response (ABR) of guinea pigs, as well as the glutathione (GSH) level, methane dicarboxylic aldehyde (MDA) level, and superoxide dismutase (SOD) activity in the cerebrum, cerebellum, and hippocampus, was determined prior to and 1, 3, 7, and 14 days after noise exposure.

RESULTSAfter noise exposure, the shifts in ABR threshold of the experimental groups were significantly higher than that of the control group (P<0.05). Compared with those in the control group, the SOD activity and GSH level both significantly decreased in the cerebrum tissue of each experimental group after noise exposure (P<0.05) and MDA content significantly increased in the 1-day group (P<0.05). As for cerebellum tissue, the SOD activity and GSH level in the 7-day group were significantly lower than those in the control group (P<0.05), but there was no difference in MDA level between each experimental group and the control group (P>0.05). In comparison with those in the control group, the GSH and MDA levels in the 1-day group after noise exposure were significantly higher, and the GSH and MDA levels in the 3-day group and the MDA level in the 7-day group after noise exposure were significantly lower (all P<0.05).

CONCLUSIONNoise exposure can lead to hearing loss and affect the antioxidant capacity of brain tissue, which indicates that the improvement in antioxidant levels may alleviate noise-induced damage.

Animals ; Antioxidants ; chemistry ; Brain ; metabolism ; Brain Chemistry ; Evoked Potentials, Auditory, Brain Stem ; Glutathione ; chemistry ; Guinea Pigs ; Male ; Malondialdehyde ; chemistry ; Noise ; adverse effects ; Superoxide Dismutase ; chemistry