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Fetal intracranial hemorrhage (FICH) is a rare clinical event of brain injury, mostly occurring in the middle and late stages of pregnancy. Because of the particularity of fetal brain structure, its pathogenesis may be related to the development of germinal layer, coagulation function and the autoregulation function of fetal intracranial vessels. FICH is often discovered by chance during routine pregnancy examinations, with atypical clinical manifestations and some patients progressing rapidly. There is no gold standard for FICH diagnosis, and the imaging manifestations are complex and varied. The diagnosis mainly relies on prenatal ultrasound and magnetic resonance imaging to assist, which needs to be distinguished from fetal intracranial tumors, Galen′s venous tumors, arachnoid cysts, and intracranial calcification. Depending on the location and extent of the hemorrhage, it can lead to varying degrees of neurological dysfunction and even death, with significant differences in prognosis. Summarize the research progress of FICH, aiming to deepen the understanding of the disease among clinical doctors, effectively improve clinical diagnosis and treatment capabilities, and reduce the birth rate of children with severe neurological sequelae while reducing the number of blindly induced abortions. [ABSTRACT FROM AUTHOR]

DOI: 10.3969/j.issn.1672-6731.2018.12.012

Objective: To investigate the value of histogram parameters in quantifying brain development trajectory at slice of anterior and posterior horns of lateral ventricles on conventional brain MRI in normal children aged 0-5 years. Methods: Routine brain MRI data [apparent diffusion coefficient (ADC) map, T 1 -weighted imaging (T 1 WI), and T 2 -weighted imaging (T 2 WI)] were retrospectively collected from 300 children aged 0-5 years who underwent MRI at Children 's Hospital of Nanjing Medical University from April 2014 to November 2021, 154 males and 146 females, aged [ M ( Q 1 , Q 3 =60) in a ratio of 8∶2. The training set was divided into 6 groups according to age:≤0.5 years, 24 persons; >0.5-≤1 years,21 persons; >1-≤2 years,31 persons; >2-≤3 years,44 persons; >3-≤4 years,42 persons; >4-≤5 years,78 persons. MRIcron software was used to delineate the whole brain at the level of the anterior and posterior horns of the lateral ventricles of the three MRI data as the region of interest. Then gray histograms and their parameters [including mean, maximum, minimum, skewness, kurtosis, mode, variance, and percentiles at 5% intervals from 10% to 95%(10th-95th) ]were obtained. Intra-class correlation coefficients (ICC) were used to assess consistency of intra-observer and inter-observer measurement. Representative parameters were selected by Spearman correlation analysis and curve fitting. The linear regression coefficient β represented development rates at different ages. The selected curve regression models were applied to the validation set, and the reliability of the model was evaluated with accuracy. n =240) and validation set ( n =60) in a ratio of 8∶2. The training set was divided into 6 groups according to age:≤0.5 years, 24 persons; >0.5-≤1 years,21 persons; >1-≤2 years,31 persons; >2-≤3 years,44 persons; >3-≤4 years,42 persons; >4-≤5 years,78 persons. MRIcron software was used to delineate the whole brain at the level of the anterior and posterior horns of the lateral ventricles of the three MRI data as the region of interest. Then gray histograms and their parameters [including mean, maximum, minimum, skewness, kurtosis, mode, variance, and percentiles at 5% intervals from 10% to 95%(10th-95th) ]were obtained. Intra-class correlation coefficients (ICC) were used to assess consistency of intra-observer and inter-observer measurement. Representative parameters were selected by Spearman correlation analysis and curve fitting. The linear regression coefficient β represented development rates at different ages. The selected curve regression models were applied to the validation set, and the reliability of the model was evaluated with accuracy. Results: Intra-observer and inter-observer histogram measurement parameters were generally in good consistency (ICC>0.800, all P <0.001). Histogram parameters ADC 10th-65th, T 1 WI 55th-80th and T 2 WI 10th-45th were highly correlated with age (∣ r ∣≥0.700, 0.600 and 0.600 respectively; all P <0.001). ADC 30th and T 2 WI 10th had the greatest goodness of fit ( R ²=0.871, 0.873; both P <0.001). Map of brain development trends showed that ADC 30th and T 2 WI 10th decreased with age. ADC 30th changed rapidly before the age of 2 years, most significantly within 6 months, and the rate of decrease slowed down after 2 years old. T 2 Histogram parameters can quantify brain developmental trajectories at slice of anterior and posterior horns of lateral ventricles on conventional MRI in normal children aged 0-5 years, and obtain the brain development curves reflecting this slice of this age group.2 WI 10th had higher accuracy in validation set [93% (56/60) and 95% (57/60), respectively]. Conclusion: Histogram parameters can quantify brain developmental trajectories at slice of anterior and posterior horns of lateral ventricles on conventional MRI in normal children aged 0-5 years, and obtain the brain development curves reflecting this slice of this age group.

Objective To report a rare case of subependymoma and explore its clinical and pathological features. Methods The clinical presentations, histopathological and immunohistochemical features of a case of subependymoma were studied retrospectively. The related literatures were also reviewed. Results A 54 ⁃ year ⁃ old male patient presented with sudden loss of awareness, generalized convulsion and transient loss of memory. Magnetic resonance imaging (MRI) showed a space ⁃ occupying lesion located in the left ventricle. The lesion was focally enhanced. Lateral ventricle was enlarged with hydrocephalus. During operation, tumor tissue was soft, grayish in colour and well circumscribed. The blood supply was moderate. The tumor nodule was resected, measuring 3 cm × 2 cm × 2 cm. Microscopically, tumor cells distributed in conglobation or group in dense fibrillary matrix of glia and many microcysts could be seen. Some eosinophilic protein fluid were accumulated in the microcysts. Tumor cells were similar in size without any atypia. Tumor cell nuclei were round or elliptical and no karyokinesis was seen. Immuohistochemistry showed glial fibrillary acidic protein (GFAP) and nestin were positively expressed in tumor cells. The Ki⁃67 labeling index was less than 1%. Neuronal nuclear antigen (NeuN) was negatively expressed. The patient was followed up for 6 months and no recurrence was found. Conclusion Subependymoma is one of the rare benign tumors of the central nervous system. High incidence appears in male adults. Its long⁃term prognosis is good after surgical complete resection. DOI：10.3969/j.issn.1672-6731.2011.01.021

Objective To combine SWI with 1H-MRS for exploring the relationship of veins and nerve cells metabolism changes of the bilateral hippocampus regions in the patients with first episode depression. Methods The subsequence of SWI and 1H-MRS was adopted to scan 20 patients with first episode depression (first episode depression group) and 20 healthy volunteers from the hospital staff or their family members (health group) in our hospital from October 2013 to October 2015 for detecting maximum diameter, length and branch numbers of the bilateral hippocampus draining veins and multiple metabolic indices (Glx, NAA, Cho, Cr and MI) of the bilateral hippocampus, finally, analyzing the correlation between them. Results Compared with the health group, the maximum diameter of left inferior ventricular vein in the first episode depression group became narrow with statistical difference (P<0.05), while the length and branch numbers were increased, but without statistically significant difference (P>0.05); the maximum diameter of right inferior ventricular vein became narrow compared with the health group, the difference was statistically significant (P<0.05), while the length and branch numbers had unobvious change without statistical difference (P>0.05). Compared with the health group, the values of Glx/Cr and NAA/Cr of left hippocampus in the first episode depression group were reduced, while the value of Cho/Cr was increased, the differences were statistically significant (t=2.69, 2.81, 2.36, P<0.05), while the value of MI/Cr had no obvious change, the differences were statistically significant (t=1.19, P>0.05); only the value of Glx/Cr in right hippocampus was reduced with statistical difference (t=2.43, P<0.05). The maximum diameter of left inferior ventricular vein was negatively correlated to the value of Cho/Cr and positively correlated to the value of Glx/Cr, NAA/Cr and MI/Cr in left hippocampus (r=0.568, 0.594, 0.095, P<0.05). Conclusion The morphological change of draining veins in hippocampus appears in the patients with first episode depression, these changes affect the nerve cell metabolism of the bilateral hippocampus, which may be one of the potential factors of first episode depression pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: To explore the neurological development of fetal with ventriculomegaly at 1 year after birth by systematically reviewing the domestic and international literature about prognosis of fetal ventriculomegaly. Methods: Wanfang database, CNKI, CBM, PubMed, EMBASE and the Cochrane Library were online searched to collect relevant literature published from January 1st, 1980 to November 22th, 2017. Literature were extracted based on the Newcastle-Ottawa Scale (NOS) , and analyzed by R software for meta-analysis. The corresponding model was selected according to the results of heterogeneity test to comprehensively analyze the prognosis of the fetus with ventriculomegaly. Results: Five studies were included in the meta analysis, all of them were of high quality (scores>5) . (1) The good prognosis rate of nervous system was 88% (95% CI :0.77-0.95) in fetus with mild ventriculomegaly, was 57% (95% CI :0.18-0.91) in those with moderate ventriculomegaly, and was 36% (95% CI :0.16-0.59) in those with severe ventriculomegaly. (2) The good prognosis rate of the nervous system was 86% (95% CI :0.75-0.94) in fetus with the isolated ventriculomegaly, while was 58% (95% CI :0.20-0.91) in those with non-isolated ventriculomegaly. The incidence of chromosomal abnormalities was 7% (95% CI :0.05-0.09) in ventriculomegaly. The improvement rate of lateral ventricle width in pregnancy was 41% (95% CI :0.27-0.57) . Conclusions: The prognosis of nervous system with mild ventriculomegaly is better than that of moderate and severe ventriculomegaly. The prognosis of nervous system with isolated ventriculomegaly is better than that of non-isolated ventriculomegaly. Fetal ventriculomegaly may be associated with fetal chromosomal abnormalities and intrauterine infection. The variation of fetal lateral ventricular width should be monitored regularly during pregnancy, the risk of poor prognosis should be informed, and pediatrician should be asked for evaluation.

Objective: To establish the system of isolation, cultivation, and identification of the neural stem cells (NSCs) from subventricular zone (SVZ) of neonatal mice so as to seek for the appropriate seed cells for potential therapeutic interventions of neurological disorders., Methods: NSCs were isolated enzymatically and mechanically from SVZ of neonatal mice and cultured. The cellular morphology was observed by inverted microscopy. Immunocytochemical stainings of anti-Nestin and anti-SOX-2 were used to identify NSCs of passage 3. To study the differentiation of NSCs, NSCs were plated into 24-wells in the medium supplemented without epidermal growth factor (EGF) and basic fibroblastic growth factor (bFGF) for 3 or 7 days. To compare the differentiation and proliferation potential of NSCs with different cultivation time, the BrdU pulse-labeling method and MTT test were used. To identify neurons and astrocytes, the anti-β-tubulin III (Tuj-1) and anti-glial fibrillary acidic protein (GFAP) staining were used., Results: The cells of the SVZ can be isolated and cultured in vitro, and these cells began to form neurospheres after cultured for 3 days at primary passage. While cultured for 7 days, these cells formed more neurospheres, and the volume of the neurospheres became bigger than neurospheres cultured for 3 days. In addition, after cultured for 7 days, the phenomena of fusion of neurospheres and adherent differentiation of neurospheres were observed under inverted microscope. These cells were provided with the typical phenotype of NSCs. The immunofluorescence staining results revealed that these cells showed positive immunoreactivity to Nestin and SOX-2. During the 4 hours BrdU pulse, the number of proliferated NSCs cultured for 3 days (75.817 ± 2.961) was significantly higher than that of NSCs cultured for 7 days (56.600 ± 4.881) (t = 3.366, P = 0.028). The results of MTT assay revealed that the absorbance (A) value of NSCs cultured for 3 days (0.478 ± 0.025) was significantly higher than that of NSCs which were cultured for 7 days (0.366 ± 0.032)(t = 2.752, P = 0.011). After cultivated without EGF and bFGF, the percentage of Tuj-1 and GFAP positive cells in NSCs was 23.1% ± 3.7% and 23.7% ± 3.8% for 3 days and was 40.1% ± 3.6% and 37.1% ± 4.5% for 7 days, respectively, all showing significant differences (t = 3.285, P = 0.030; t = 3.930, P = 0.017)., Conclusion: The NSCs from SVZ of neonatal mice have potentials of self-renewal and multipotential differentiation in vitro. With different cultivation time, the potentials of proliferation and differentiation of NSCs are different.

The purpose of this study is to explore the fate and effect of human embryonic neural stem cells (hNSCs) after transplantation into ipsilateral lateral ventricle of stroke rats. Adult rats were exposed to one-hour transient middle cerebral artery occlusion (MCAO), and then hNSCs were transplanted into ipsilateral lateral ventricle 7 days after reperfusion. Infarct volume was calculated by cresyl violet staining. The improvements of neural functions were assessed by behavioral tests. Immunofluorescence staining was performed to observe the migration and differentiation of transplanted hNSCs. The results showed that transplanted hNSCs significantly reduced ischemia-induced infarction in MCAO rats, and improved neural functional restoration when assessed by rotarod, footfault and corner-turn tests. The grafted cells migrated predominantly to several specific brain regions, such as corpus callosum and peri-infarct area. Furthermore, these cells differentiated into oligodendrocytes and astrocytes in corpus callosum, and neurons in peri-infarct parenchyma. These results suggest that transplanted hNSCs through lateral ventricle of the ischemic side may exert effective therapeutic effects on stroke rats via migration and differentiation in specific brain regions.

Objective: To explore the relationship between nitric oxide (NO) in central nervous system and exercise-induced fatigue stress and to study the effect of L-arginine (L-Arg), as a substrate of nitric oxide, on the exercise capacity and NO content in the exhausted rat brain and blood., Methods: Through an implanted cannula, the normal saline or L-Arg was microinjected into rat's intracerebroventrical for consecutive four days. Then an acute exhaustive model (on the speed of 18 m/min, an inclination of 5 degrees) was established with animal treadmill. The time of exercise till exhaustion was recorded, and the total workload was calculated that represented the exercise capacity. Nitrate and nitrite (NO3/NO2-, NOx-) levels in blood, hypothalamus and hippocampus were assayed., Results: Both the time of exercise till exhaustion and total workload in the LArg group increased respectively by 51.8% and 50.08% (P < 0.05), compared with those in the control. The NOx- content in hypothalamus in the L-Arg group (8.93 +/- 1.83) micromol/g pro was larger than that in the control (4.25 +/- 0.79) micromol/g pro, (P < 0.01). There was no significant difference in NOx- content in brain and hippocampus between the two groups. The total workload was positively correlated with NOx- concentration in hypothalamus (P < 0.01). However, there was no correlation between workload and changes in hippocampus NOx- content at fatigue., Conclusion: Intracerebroventricular microinjection of L-Arg may enhance the exercise capacity and lead to up-regulation of NO by means of L-Arg-NO signal path in the hypothalamus. Hypothalamus may be a key site in brain in the modulation of physiological exercise.

Objective: To observe the effect of intracerebroventricular injection of rAAV-HIF-1α on hippocampal neuronal apoptosis in a rat model of Alzheimer disease (AD)., Methods: Thirty-two male SD rats (250-300 g) were randomized into 4 groups (n=8), including the normal control group without any treatment, AD model group with right intracerebroventricular injection of 2 µl Aβ25-35 (10 mg/m1), sham-operated group with right intracerebroventricular injection of 2 µl normal saline, and AD+ rAAV-HIF-1α group with right intracerebroventricular injection of 10 µl rAAV-HIF-1a (1×10¹² v.g./m1) one week after Aβ25-35 injection. The rats were sacrificed to detect the expression of HIF-1α and apoptosis of hippocampal neurons 5 weeks after Aβ25-35 or saline injection., Results: Western blotting showed that the expression of HIF-1α was significantly higher in AD+rAAV-HIF-1α group (451.59±34.39) than in normal control group (229.05±41.28) and sham-operated group (216.29±37.08) (P<0.05) without significant difference between the latter two groups. The apoptotic ratio of the hippocampal neurons was significantly higher in AD model group ([19.49±2.59]%) than in normal control group ([5.41±0.75]%) and sham-operated group ([5.28±0.66]%) in (P<0.05), and intracerebroventricular injection of rAAV-HIF-1α resulted in a significant reduction of the apoptotic ratio in the AD rats ([12.07±2.06]%) (P<0.05)., Conclusion: Intracerebroventricular injection of rAAV-HIF-1α can inhibit hippocampal neuronal apoptosis in the rat model of AD.

Objective: To investigate the effects of brain-derived neurotrophic factor (BDNF) on survival, migration and differentiation of neural stem cells (NSCs) transplanted into the brain of newborn rats with hypoxic-ischemic brain damage and the recovery of nervous functions., Methods: The NSCs were separated from hippocampus of neonatal Wistar rats within 24 h after birth. Brdu, NSE and GFAP were used as markers of differentiation and proliferation of NSCs. The newborn rats were subjected to hypoxic-ischemic condition to induce brain damage. Seven days later, NSCs transplantation was performed for the animals. The rats were divided into normal control group, HIBD group, PBS group, NSCs transplantation group, BDNF group and BDNF + NSCs transplantation group randomly. At 4 weeks after transplantation the nervous function of rats was observed by Y-maze and nerve behavior test. After they were sacrificed, the rat brains were examined by immunocytochemistry for Brdu and by immunofluorescence for NSE/Brdu., Results: The hippocampus NSCs of newborn rat could be well cultured and they expressed nestin and they could differentiate into NSE, GFAP. Most of NSCs survived in cerebral ventricle 4 weeks after transplantation in brain through Brdu immunocytochemistry and they migrated into regions of brain extensively, especially to the injured side of cortex and hippocampus. The number of living NSCs in the injured side of cortex and hippocampus of BDNF + NSCs transplantation group increased evidently and the percentage of NSCs differentiated into NSE was higher than that in the NSCs transplantation group (P < 0.05). The nerve function recovery of the rats in BDNF and NSCs treated group was significantly better than that in the other groups (P < 0.05). The NSCs group had no prominent changes as compared with the model groups (P > 0.05)., Conclusions: NSCs can be isolated from newborn rats hippocampus and cultured in vivo. NSCs can survive, migrate and differentiate into neurons through cerebral ventricle. BDNF could significantly accelerate proliferation and differentiation of NSCs transplanted into the brain of rats with HIBD. The nervous function recovery was improved prominently by transplantation of NSCs with BDNF application, which may become a potentially effective method to treat HIBD.

Objective: To investigate the duration of tau hyperphosphorylation and spatial memory retentive deficit induced by single injecting with Forskolin, a protein kinase A activator, into lateral ventricle of rats, and the correlation between the two pathological alterations., Methods: Forskolin (80 micromol/L, 40 microl) was injected into the lateral ventricle by stereotaxic injection. Tau phosphorylation and spatial memory retention were measured by Western blot/immunocytochemistry and Morris-Water-Maze test, respectively., Results: The phosphorylation levels of tau at Tau-1, PHF-1, and pS214 epitopes were significantly elevated at 24, 48 and 72 h after single administration of Forskolin (P < 0.05). The most significant elevation was seen at 48 h (P < 0.01) and it tended to recover at 72 h (P < 0.05) after injection. The correlation between the two pathological alterations was positive at PHF-1 site (r = 0.97, P < 0.05), negative at Tau-1 site (r = -0.963, P < 0.05), and not significant at pS214 site (r = 0.705, P > 0.05)., Conclusions: Forskolin can induce tau hyperphosphorylation and spatial memory retentive deficit within a certain period of time. The level of tau phosphorylation in hippocampus is somehow correlated with the spatial memory deficit in rats.

Aim: To investigate whether the selective AT1 receptor antagonist irbesartan exerts neuroprotective effect on focal cerebral ischemia in normotensive rats., Methods: Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion, with the monitoring of laser Doppler flowmetry. To avoid the interaction with peripheral AT1 receptors, irbesartan was infused intracerebroventricularly (ICV) at a dose which effectively inhibited brain- but not vascular AT1 receptors. Neurological status was evaluated daily after MCAO. Rats were killed and brain samples were collected for the measurement of infarct size and immunohistochemical evaluation of apoptosis by deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling (TUNEL) and expression of activated Caspase-3 and the cleavage fragment of poly (ADP-ribose) polymerase (PARP)., Results: Treatment with irbesartan improved significantly the neurobehavioral functions after cerebral ischemia. The infarct size was reduced about 42% on day 7 after MCAO (P < 0.05). Meanwhile,irbesartan treatment significantly decreased the number of TUNEL-positive cells in the penumbra. The expression of activated Caspase-3 and the downstream cleavage fragment of poly (ADP-ribose) polymerase in the penumbra were also inhibited by irbesartan therapy on day 3 after transient cerebral ischemia., Conclusion: Angiotensin AT1 receptor antagonist exhibits neuroprotection against transient cerebral ischemia in the brain. The neuroprotective effects in ischemic tissue may be associated with its inhibition of apoptotic cell death in the penumbra.

Aim: To investigate the effect of selective H3 receptor agonist(R)-alpha-methylhistamine and antagonist thioperamide on the respiratory response in asthmatic guinea pigs respectively., Methods: Anesthesized guinea pigs were prepared with a implanted intracerebroventricular (icv) cannula and instrumented for the measurement of respiratory rate (RR) and diaphragmatic electric activity (DA). Substance P-like immunoreactive (SP-LI) substances in lower respiratory tract were detected by immunohistochemical method. Brain histamine contents were measured by fluorometric determination., Results: (1) Intravenous injection of ovalbumin caused tachypnea and significant decrease in DA magnitude. At the same time, SP-LI substances increased in trachea, bronchus and lung. (2) Administration of selective H3 receptor agonist (R)-alpha-methylhistamine (5 microg) icv immediately after i.v. ovalbumin could significantly ameliorate the changes in RR and DA induced by ovalbumin. In accordance, SP-LI substances in lower respiratory tract markedly decreased at 5 min and 10 min after (R)-alpha-methylhistamine microinjection. (3) Icv thioperamide (20 microg) caused a significant increase in RR and a decrease in DA. (4) Brain histamine contents increased in hypothalamus and cortex during asthma. After microinjection of thioperamide (20 microg) icv significant increase of histamine contents in hypothalamus and cortex was observed., Conclusion: Brain histamine H3 receptors may be related to asthmatic respiratory responses.

Aim: To investigate the role of intracerebroventricular (icv) injection substance P(SP) in cardiovascular regulation and the relationship with noradrenergic system., Methods: Rabbits anesthetized with urethane were intracerebroventricularly given SP in presence or absence of phentolamine, prazosin, yohimbine. Cardiovascular responses including heart rate (HR), mean arterial blood pressure (MAP), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the maximum velocity of ascending or descending in intraventricular pressure (+/- dp/dt(max)) and the maximum shortening velocity(Vpm) of myocardial contractile element were recorded, and changes of NA content in cerebrospinal fluid (CSF) were determined in rabbits with icy injection of SP., Results: (1) icv SP elicited significant increased of HR, MAP, LVSP, LVEDP, + dp/dt(max), -dp/dt(max), Vpm and the levels of NA in intracisternal CSF 30 min after injection. (2) Pretreatment with phentolamine, prazosin, but not yohimbine, attenuated icv SP-induced cardiovascular responses compared with controls (P < 0.05)., Conclusion: (1) icv SP can produce positive inotropic and chronic response in myocardium and pressor response in intact rabbits. (2) alpha1 adrenoceptors may be involved in the cardiovascular responses to icy SP. (3) Central administration of SP can increase the release of NA or inhibit reuptake of NA, which may be responsible for an important mechanism of SP-potentiated cardiovascular responses in brain.

Aim: To explore the effect of central serotonin (5-hydroxytryptamine, 5-HT) on gastric motility in rabbit and to analysis its mechanism., Methods: Intracerebroventricular (icv) microinjection of drugs were used. The frequency and the amplitude of contractions of gastric motility were recorded., Results: (1) Injection (icv) of 25 microg 5-HT increased the amplitude of contractions and decreased the frequency of gastric motility. (2) The effects of 5-HT were inhibited by injection (icv) of atropine, but intravenous(iv) injection of atropine could only block the increase effect of 5-HT on intragastric pressure. After injection (icv or iv) of phentolamine or propranolol, the effects of 5-HT on gastric motility were not changed markedly. (3) Microinjection (icv) of naloxone or diphenhydramine inhibited the inhibitory effect of 5-HT on the frequency of gastric contractions, and the diphenhydramine reversed the increase effect of 5-HT on intragastric pressure. (4) Vagotomy abolished the effects of 5-HT completely., Conclusion: There may be different nerve mechanisms in regulation of central 5-HT on the frequency and amplitude of contractions of gastric motility. The increase effect of 5-HT on intragastric pressure is medicated by the cholinergic system in brain, and histamine may be one of the important element on the effect of 5-HT. The cholinergic fibers in vagus nerve transmit the effect. The inhibitory effect of 5-HT on the frequency of contractions is also medicated by activating the cholinergic system in brain, enkephalin and histamine are also involved, and it is transmitted via noncholinergic and nonadrenergic fibers in vagus nerve.

The changes in carotid sinus baroreceptor reflex (CSR) performance induced by intracerebroventricular injection (i.c.v.) of histamine (HA) were investigated. The effects of pretreatment with HA receptors antagonists into the cerebroventricle or nucleus of solitary tract (NTS) on the responses of CSR to HA were also examined. Intracarotid sinus pressure (ISP)-mean arterial pressure (MAP) relationship curve was constructed by fitting to the logistic function with five parameters in 50 Wistar rats anesthetized with pentobarbital sodium. The left and right carotid sinus regions were isolated from the systemic circulation and the ISP was altered in a stepwise manner. The main results obtained are as follows. (1) i.c.v. injection of HA (100 ng) significantly shifted the ISP-MAP relationship curve upwards and moved the middle part of ISP-Gain relationship curve downwards, and reduced the MAP range and maximum gain (G(max)), but increased the threshold pressure (TP), saturation pressure (SP) and ISP at G(max) (ISP (Gmax)). (2) The pretreatment with H(1) or H(2) receptors antagonist, chlorpheniramine (CHL, 5 microg) or cimetidine (CIM, 15 microg), could obviously diminish the above-mentioned changes in CSR performance induced by HA, but the effect of CIM was less remarkable than that of CHL. (3) The pretreatment with both CHL and CIM (5 microg and 15 microg) at the same time abolished the responses of CSR performance to HA completely. (4) After microinjection of CHL (0.5 microg) or CIM (1.5 microg) into the NTS, the responses of CSR to HA were similar to those after i.c.v. CHL or CIM, but the change in TP was significantly decreased. These findings suggest that the intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity. The response of CSR to HA might be mediated by both central H(1) and H(2) receptors, especially by H(1) receptors. The effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to NTS. It is suggested that the HA receptors in the NTS play an important role in the responses of CSR to HA.