This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.
Animals ; Aquaporin 4/genetics* ; Astrocytes ; Brain Edema/drug therapy* ; Brain Ischemia/metabolism* ; Flavonoids ; Infarction, Middle Cerebral Artery/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; TRPV Cation Channels/therapeutic use*

PURPOSE: Hypertonic fluids such as mannitol and half-molar sodium lactate are given to treat intracranial hypertension in patients with severe traumatic brain injury (TBI). In this study, sodium lactate was compared to mannitol in patients with TBI to investigate the efficacy in reducing intracranial pressure (ICP). METHODS: This study was a systematic review with literature research on articles published in any year in the databases of PubMed, ScienceDirect, Asian Journal of Neurosurgery, and Cochrane Central Register of Controlled Trials. The keywords were "half-molar sodium lactate", "mannitol", "cerebral edema or brain swelling", and "severe traumatic brain injury". The inclusion criteria were (1) studies published in English, (2) randomized control trials or retrospective/prospective studies on TBI patients, and (3) therapies including half-molar sodium lactate and mannitol and (4) sufficient data such as mean difference (MD) and risk ratio (RR). Data analysis was conducted using Review Manager 5.3. RESULTS: From 1499 studies, a total of 8 studies were eligible. Mannitol group reduced ICP of 0.65 times (MD 0.65; p = 0.64) and improved cerebral perfusion pressure of 0.61 times (MD 0.61; p = 0.88), better than the half-molar group of sodium lactate. But the half-molar group of sodium lactate maintained the mean arterial pressure level of 0.86 times, better than the mannitol group (MD 0.86; p = 0.09). CONCLUSION Half-molar sodium lactate is as effective as mannitol in reducing ICP in the early phase of brain injury, superior over mannitol in an extended period. It is able to prevent intracranial hypertension and give better brain tissue perfusion as well as more stable hemodynamics. Blood osmolarity is a concern as it increases serum sodium.
Brain Edema ; Brain Injuries, Traumatic/drug therapy* ; Diuretics, Osmotic/therapeutic use* ; Humans ; Intracranial Hypertension/etiology* ; Intracranial Pressure ; Mannitol/therapeutic use* ; Prospective Studies ; Retrospective Studies ; Saline Solution, Hypertonic ; Sodium Lactate

OBJECTIVE: To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury. METHODS: Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting. RESULTS: Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01). CONCLUSIONS Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
Animals ; Brain Edema ; drug therapy ; etiology ; Brain Injuries, Traumatic ; complications ; drug therapy ; Gene Expression Regulation, Enzymologic ; drug effects ; Indazoles ; pharmacology ; therapeutic use ; MAP Kinase Signaling System ; drug effects ; Matrix Metalloproteinase 9 ; genetics ; Piperazines ; pharmacology ; therapeutic use ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Choroid plexus tumors are uncommon brain tumors that primarily occur in children. Most of these tumors originate from the intraventricular area, and the most common clinicalpresentation is increased intracranial pressure. Dissemination through the cerebrospinal fluid space is the inevitable natural course of the disease. Here, we present 2 rare cases of adult choroid plexus carcinoma (CPC), each with distinct clinical presentation and progression. The first case was a 40-year-old male who presented with multiple intraventricular masses. After surgical biopsy, radiation and intrathecal chemotherapy failed to elicit any response. The patient progressed with spinal cord dissemination and expired 1 year later. The second case presented with visual disturbance, and brain MRI revealed a large ovoid juxtaventricular mass with peritumoral edema. This 49-year-old female patient underwent craniotomy for what was thought to be a high-grade glioma; however, the mass was connected to the choroid plexus at the operative field. Her pathology specimen was diagnosed as CPC, and adjuvant systemic chemotherapy was administered. She has now been free of recurrence for 10 months. The description of the presentation and progression of these rare adult-onset CPC provides insight for the diagnosis and treatment of other rare instances of choroid plexus tumors.
Adult ; Biopsy ; Brain ; Brain Neoplasms ; Cerebrospinal Fluid ; Child ; Choroid Plexus Neoplasms ; Choroid Plexus ; Choroid ; Craniotomy ; Diagnosis ; Drug Therapy ; Edema ; Female ; Fourth Ventricle ; Glioma ; Humans ; Intracranial Pressure ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pathology ; Recurrence ; Spinal Cord

Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage (SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury (EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine (10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier (BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1β, IL-6, TNF-α, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.
Animals ; Apoptosis ; drug effects ; Blood-Brain Barrier ; drug effects ; Brain Edema ; drug therapy ; etiology ; Cytokines ; genetics ; metabolism ; Disease Models, Animal ; Fluoxetine ; pharmacology ; therapeutic use ; In Situ Nick-End Labeling ; Male ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Pain Measurement ; Psychomotor Performance ; drug effects ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; drug therapy ; pathology ; Time Factors ; Vasospasm, Intracranial ; drug therapy ; etiology

The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury (TBI) and the potential mechanisms related to the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) pyrin domain-containing 3 (NLRP3) inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier (BBB) integrity, the neurological function and histological injury were assessed, at the same time, the mRNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein (ASC) and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.
Animals ; Benzimidazoles ; administration & dosage ; Benzoates ; administration & dosage ; Blood-Brain Barrier ; drug effects ; Brain Edema ; drug therapy ; genetics ; pathology ; Brain Injuries, Traumatic ; drug therapy ; genetics ; pathology ; Caspase 1 ; biosynthesis ; Gene Expression Regulation ; drug effects ; Humans ; Inflammasomes ; adverse effects ; genetics ; Interleukin-18 ; biosynthesis ; Interleukin-1beta ; biosynthesis ; Male ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; biosynthesis ; genetics ; Signal Transduction ; drug effects

To investigate the effects of triptolide on inflammation and apoptosis induced by focal cerebral ischemia/reperfusion in rats.The rat model of focal cerebral ischemia/reperfusion injury was established according to Longa's method. A total of 80 SD rats were randomly divided into 5 groups:normal control, sham group, DMSO group, middle cerebral artery occlusion (MCAO) group, and MCAO with tripolide treatment group. TTC staining was used to examine the site and volume of cerebral infarction, and Longa score was employed for neurological disorders measurement. Number of astrocytes was measured by fluorescence staining, and neuronal apoptosis was determined by TUNEL staining. The expressions of inducible nitric oxide synthase(iNOS), cyclooxygenase 2(COX-2) and NF-κB proteins were detected by immunohistochemistry, and the expression of iNOS, COX-2 mRNA was detected by real-time PCR.Compared with DMSO group and MCAO group, brain edema was improved (80.03±0.46)% (<0.05), infarct volume was reduced (8.3±1.4)% (<0.01), Longa score was decreased (1.38±0.20,<0.05) in triptolide treatment group. Meanwhile triptolide also dramatically reduced the number of GFAP-positive astrocytes (<0.05), alleviated protein expression of COX-2 (91.67±1.31), iNOS (95.24±5.07) and NF-κB (75.03±2.06) triggered by MCAO (all<0.05), and induced a down-regulation of cell apoptosis as showed by TUNEL assay (64.15±3.52,<0.05).Triptolide can reduce the cerebral infarction volume, attenuate brain edema and ameliorate the neurological deficits induced by cerebral ischemia-reperfusion injury rats, indicating that it might be used as a potential anti-inflammatory agent.
Animals ; Apoptosis ; drug effects ; Astrocytes ; Brain Edema ; drug therapy ; Brain Injuries ; chemically induced ; drug therapy ; Brain Ischemia ; chemically induced ; Cyclooxygenase 2 ; drug effects ; Diterpenes ; pharmacology ; Down-Regulation ; drug effects ; Epoxy Compounds ; pharmacology ; Infarction, Middle Cerebral Artery ; chemically induced ; drug therapy ; Inflammation ; drug therapy ; Male ; NF-kappa B ; drug effects ; Nitric Oxide Synthase Type II ; drug effects ; Phenanthrenes ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; chemically induced ; drug therapy

OBJECTIVETo study and evaluate the curative effect and mechanism of Qiangxin Granule (QXG) in intervening chronic heart failure (CHF) rats with Xin-qi deficiency complicated blood stasis and edema syndrome (XQD-BS-ES).

METHODSTotally 72 SD rats of clean grade were randomly divided to the normal control group (n =10) and the model group (n = 62). The XQD-BS-ES rat model was established by adriamycin plus propylthiouracil method. Survived modeled rats were then randomly divided to 5 groups i.e., the model group (n = 11, administered with normal saline by gastrogavage), the Western medicine (WM) group (n =11 , administered with perindopril and hydrochlorothiazide by gastrogavage), the low dose QXG (QXG(L)) group (n = 11, administered with 9.26 g/kg QXG by gastrogavage), the middle dose QXG (QXG(M)) group (n = 11, administered with 18.52 g/kg QXG by gastrogavage), the high dose QXG (QXG(H)) group (n = 11, administered with 37.04 g/kg QXG by gastrogavage). After 4 weeks of treatment, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), brain natriuretic peptide (BNP), heart rate (HR), respiratory rate (RR), urine output, ear temperature, exhaustive swimming test (EST), tri-iodothyronine (T3), tetra-iodothyronine (T4), thyroid stimulating hormone (TSH), as well as heart, lung, liver weight index and their pathological sections, and high sensitivity C-reactive protein (HS-CRP), angiotensin II (Ang II), carbohydrate antigen 125 (CA125) were detected and compared.

RESULTSCompared with the normal control group, LVEF, LVFS, BNP, HR, RR, urine output, ear temperature, EST, T3, T4, TSH, HS-CRP, Ang II, and CA125 changed significantly in the model group (P < 0.01). Compared with the model group after treatment, LVEF, LVFS, BNP, urine output, EST, T4, heart and liver weight index, HS-CRP, Ang II, CA125 were significantly improved in each QXG group (P < 0.05, P < 0.01). Moreover, TSH was improved in the QXGL and QXG(M) groups (P < 0.05); ear temperature and T3 in the QXG(M) were also improved (P < 0.05); the lung weight index decreased in the QXG(M) and QXG(H) groups (P < 0.01). Compared with the WM group, T4 and CA125 were obviously improved in all QXG groups (P < 0.01); BNP and ear temperature were obviously improved in QXG(L) and QXG(M) groups (P < 0.05, P < 0.01); LVEF, LVFS and TSH were obviously improved in the QXG(M) group (P < 0.05, P < 0.01). And as far as each treatment group, LVEF, LVFS, urine output increased significantly after treatment (P < 0.01); EST obviously increased in QXG(M) and QXG(H) groups (P < 0.01); ear temperature increased in all QXG groups (P < 0.05, P < 0.01). Moreover, compared with the model group, pathological changes of heart, lung, and liver were improved to some degree in each treatment group, especially in the QXG(M) group.

CONCLUSIONSGood curative effect was shown in each QXG group. QXG could improve LVEF, LVFS and BNP of CHF rats of XQD-BS-ES, as well as T3, T4, TSH, EST, urine output, and ear temperature. Moreover, QXG showed superiority than WM group in this respect.

Angiotensin II ; Animals ; C-Reactive Protein ; Chronic Disease ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Edema ; Heart ; Heart Failure ; drug therapy ; Heart Ventricles ; Medicine, Chinese Traditional ; Natriuretic Peptide, Brain ; Qi ; Rats ; Rats, Sprague-Dawley ; Syndrome ; Thyrotropin ; Ventricular Function, Left

OBJECTIVETo investigate the protective effect of Apelin-13 on focal cerebral ischemia-reperfusion injury in rats.

METHODSFocal transient cerebral ischemia-reperfusion injury was induced in male SD rats using modified suture occlusion technique. The rats were randomly divided into 5 groups: Sham group, Model group, Apelin-low dose (A) group, Apelin-middle dose (B) group and Apelin-high dose (C) group. Apelin-13 was injected into lateral cerebral ventricle, and the neurological function score, brain edema, infarct volume, apoptosis, malondialdehyde (MDA), superoxide dismutase (SOD) and extracellular regulated kinase1/2 (ERK1/2) protein were measured.

RESULTSNeurological function scores, percentage of brain water content, infarct volumes and TUNEL-positive cells in B and C groups were lower than those in Model group (P<0.05). The level of MDA in the tissue bomogenate of brain tissue in the surrounding area of ischemia of B and C groups was lower than that of Model group, while the activity of SOD was higher (P<0.05). There was no significant difference in ERK1/2 protein expression among the groups (P>0.05). P-ERK1/2 increased in Model group and A, B, and C groups compared with Sham group (P<0.05), and that of A, B, and C group was higher than that of Model group (P<0.05).

CONCLUSIONApelin-13 may play an important role by inhibiting oxidative stress to protect against focal cerebral ischemia-reperfusion injury; ERK1/2 signaling pathway may be involved in the protective mechanism of Apelin-13.

Animals ; Apoptosis ; Brain Edema ; Brain Ischemia ; drug therapy ; Intercellular Signaling Peptides and Proteins ; pharmacology ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; Signal Transduction ; Superoxide Dismutase ; metabolism

Adult ; Aged ; Bevacizumab ; therapeutic use ; Brain Neoplasms ; drug therapy ; therapy ; Edema ; drug therapy ; etiology ; Female ; Humans ; Male ; Middle Aged ; Re-Irradiation ; adverse effects