As a severe threat to human health, ischemic brain injury has a very complex pathological mechanism involving excitotoxic amino acids, oxygen free radical formation, nitric oxide (NO), Ca2+ overload and inflammation. Traditional Chinese medicine Qingkailing injection have shown good clinical efficacy in the treatment of cerebrovascular disease, and thus it is very significant to studies on its pharmacological mechanism. This essay summarizes relevant studies on pharmacological mechanism of a new compound traditional Chinese medicine Jingzhiqiangkailing (JZQKL) injection in treatment on cerebral ischemia, and explains the pharmacological mechanism of its single effective compounds and their compatibility in treatment of schemic brain injury in the aspects of regulating inflammatory response, neurotrophic factors, vascular protection, blood-brain barrier (BBB) protection and others, and thus providing information for further studies.
Animals ; Blood-Brain Barrier ; drug effects ; Brain Ischemia ; drug therapy ; Cell Adhesion Molecules ; physiology ; Cytokines ; biosynthesis ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Injections ; Nerve Growth Factors ; physiology

OBJECTIVETo investigate the effects of preconditioning and postconditioning with Shenfu Injection (SFI) on cognitive function in patients after valve replacement under extra-corporeal circulation.

METHODSThirty-two patients prepared to receive valve replacement, aged 25-54 years, with heart function of II-III level, were randomly assigned to four groups, eight in each group. Patients in group E1 received SFI 1 mL/kg after intubation and before blocking the aorta; patients in group E2 received SFI 1 mL/kg after opening the aorta; patients in group E3 received SFI 0.5 mL/kg twice, at before blocking and after opening the aorta, respectively; and patients in group C received 1 mL/kg normal saline after intubation for control. All the medication was infused via pump. Venous blood samples were taken from the internal jugular venous bulb cannula for detecting plasma S100beta protein by ELISA at 6 different time points, i.e. after trachea intubation (T1), 10 min after cardiopulmonary bypass (CPB, T2), hypothermia stabilizing stage (T3), re-warming to 33 degrees C (T4), ending CPB (T5) and 1 h after ending CPB (T6). And patients' cognitive function was assessed for 4 times with mini-mental state examination (MMSE) scale, at the day before operation, and 1, 2, 7 days after operation.

RESULTSThe elevation of S100beta plasma protein was lesser in the three E groups than that in group C (P < 0.05), and the lowest level was shown at T6 in Group E3 (P < 0.05). The highest incidence of cognitive dysfunction occurred in Group C one week after operation (P < 0.05).

CONCLUSIONSFI may reduce the plasma level of S100B protein, maintain stable the structure and function of blood-brain barrier, it is favorable to the post-operational recovery of neurological function of patients, showing good brain protective effect. The optimal effect could be obtained by pump infusion of 0.5 mL/kg of SFI before aortic blocking and after aortic opening.

Adult ; Blood-Brain Barrier ; drug effects ; Brain ; blood supply ; Cardiopulmonary Bypass ; Cognition Disorders ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Valve Prosthesis Implantation ; Humans ; Ischemic Preconditioning ; Male ; Middle Aged ; Nerve Growth Factors ; blood ; Phytotherapy ; Postoperative Complications ; prevention & control ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; blood

PURPOSE: Traumatic brain injury is a multifaceted injury that involves direct mechanical damage, intraparenchymal and subarachnoid hemorrhage, breakdown of the blood-brain barrier, excitotoxicity, and ischemia. Even though much investigations were performed, acceptable mechanical informations were rare. The aim of this study was to reveal the expression pattern of intermediate filament proteins associated with gliotic scars in cerebral cortex of rats after cryoinjury. METHODS: A total of 18 male Sprague-Dawley rats weighing 300 g, 2 months old, were used throughout the experiments. To injure the brain, rats were anesthetized for surgery with 3.5% chloral hydrate(1 mL/100 g, intraperitoneally); the frontal bones were exposed by elevating the skin; and craniectomies were performed adjacent to the central suture, midway between lambda and bregma. A cryoinjury was then created by applying a cold probe(3-mm-diameter steel rod chilled in liquid nitrogen) to the left frontal cortex(ipsilateral cortex) for 1 min. Rats were sacrificed at 1, 4, 7 and 14 days postsurgery(n=3, per time point), and three rats were sacrificed as normal controls. Serial brain cryosections were made by cryostat. For immunohistochemistry, brain tissue sections were allowed to react with mouse anti-rat GFAP antibody(1:200), mouse anti-rat vimentin antibody(1: 200), and mouse anti-rat nestin antibody(1:200). RESULTS:Reactive astrocytes expressing GFAP, vimentin and nestin appeared for the first time at 6 hours after cryoinjury. Proliferation of GFAP and nestin positive cells started at 1 day after cryoinjury, reached its maximum on day 4, and returned to normal level after the 7th post-injured day. Proliferation of vimentin positive cells started at 1 day after cryoinjury, reached its maximum on day 4, and returned to normal level after the 14th post-injured day. Characteristic morphological changes in reactive astrocytes were seen at 4 days after cryoinjury. CONCLUSION: The above results suggest that GFAP, vimentin and nestin positive cells attend in the formation of gliotic scars.
Animals ; Astrocytes ; Blood-Brain Barrier ; Brain ; Brain Injuries ; Cerebral Cortex ; Chloral Hydrate ; Cicatrix ; Cold Temperature ; Frontal Bone ; Humans ; Immunohistochemistry ; Intermediate Filament Proteins ; Intermediate Filaments ; Ischemia ; Male ; Mice ; Nerve Tissue Proteins ; Rats ; Rats, Sprague-Dawley ; Steel ; Subarachnoid Hemorrhage ; Sutures ; Vimentin

Neurolymphomatosis, which is defined as a peripheral nerve infiltration of lymphoma, is an infrequent complication of systemic lymphoma and the isolated involvement of the peripheral nerve as a sign of recurrence is very rare. Here, we report a case with neurolymphomatosis presented as a mononeuropathy multiplex and is the first reported case in Korea. With potent chemotherapy, the blood-nerve barrier may have a critical role in the isolated recurrence of lymphoma in the peripheral nervous system.
Animals ; Blood-Nerve Barrier ; Drug Therapy ; Korea ; Lymphoma ; Lymphoma, B-Cell ; Marek Disease* ; Mononeuropathies* ; Peripheral Nerves ; Peripheral Nervous System ; Recurrence

BACKGROUNDNeurone atrophy and loss are major causes of chronic neurodegenerative disorders such as Alzheimer's disease. Despite many pharmacotherapies for neurodegeneration, there are no accepted treatments. We investigated the feasibility of human nerve growth factor beta (hNGFbeta) gene expression mediated by recombinant adeno-associated viruses type-2 (rAAV-2) vector in the central nervous system (CNS) after blood brain barrier (BBB) disruption.

METHODSrAAV-2 containing hNGFbeta gene was constructed. The ability of hNGFbeta gene mediated by rAAV-2 vector (rAAV-2/hNGFbeta) to transfect cells in vitro was confirmed by both ELISA and bioassay of hNGFbeta in the culture supernatant of BHK-21 cells infected by rAAV-2/hNGFbeta. rAAV-2/hNGFbeta and rAAV-2/green fluorescence protein (GFP) were administrated separately to rat brains through internal carotid intubation after BBB disruption with hypertonic mannitol. Brain hNGFbeta concentration was measured by ELISA and GFP in brain sections was examined by laser scan confocal microscope.

RESULTSAfter 48 hours, hNGFbeta content in supernatant was up to (188.0 +/- 28.6) pg/ml when BHK-21 cells were infected by rAAV-2/hNGFbeta at multiplicity of infection (MOI) 1.0 x 10(6) vector genome. Neurone fibre outgrowths were obvious in dorsal root ganglion neurone assays by adding serum free culture medium harvested from BHK-21 cells exposed to rAAV-2/hNGFbeta. Whole brain hNGFbeta content in rAAV-2/hNGFbeta transferred group was up to (636.2 +/- 140.6) pg/ml. hNGFbeta content of BBB disruption in rAAV-2/hNGFbeta infused group increased significantly compared to the control group (P <0.05). GFP expression was clearly observed in brain sections of rAAV-2/GFP transferred group.

CONCLUSIONrAAV-2/hNGFbeta successfully expresses in the CNS after BBB disruption induced by hypertonic mannitol.

Animals ; Blood-Brain Barrier ; Brain ; metabolism ; Cricetinae ; Dependovirus ; genetics ; Genetic Vectors ; genetics ; Humans ; Nerve Growth Factor ; genetics ; Recombination, Genetic

BACKGROUND: Minocycline, a semisynthetic second-generation tetracycline, is an antibiotic that has excellent ability to penetration into the CNS via the brain-blood barrier. Minocycline has emerged as a potent inhibitor of microglial activation, and it is an effective neuroprotective agent in experimental brain ischemia. Glial cell activation and proliferation are known to be associated with neuropathic pain in the peripheral nerve injuries. METHODS: The fifty percent threshold of withdrawal responses was measured in the hindpaws of SD rats following tight ligation of left fifth lumbar spinal nerve. Rats were sacrificed at 1, 3, 5, and 7 days and at 0.5, 1, 2, and 4 h post ligation (n=5/group/time point). Immunohistochemistry for GFAP, CD11b and c-Fos was done on the spinal cord at the level of the fifth lumbar nerve. Minocycline (45 mg/kg) and normal saline (300-400 microL) were administered intraperitoneally, 1 day and 1 h before the operations, and every day postoperatively until the rats were sacrificed. RESULTS: Treatment with minocycline reduced allodynia and the expressions of CD11b at 5 days and c-Fos at 1 and 2 h post operation compared with the saline treatment (control). CONCLUSIONS: It was thought that minocycline reduced the allodynia induced by tight ligation of the fifth lumbar spinal nerve in rats through the inhibition of microglial activation and c-Fos expression.
Animals ; Blood-Brain Barrier ; Brain Ischemia ; Horns* ; Hyperalgesia* ; Immunohistochemistry ; Ligation ; Microglia ; Minocycline* ; Neuralgia ; Neuroglia ; Peripheral Nerve Injuries ; Rats* ; Spinal Cord ; Spinal Nerves ; Tetracycline

AIMTo study the permeability of nerve growth factor (NGF) liposomes (NGF-L, NGF-SSL, NGF-SSL-T) on the blood-brain barrier (BBB) model and the distribution in vivo, and analyze the correlation between the results in vitro and in vivo.

METHODSThe BBB model in vitro was established by using mouse brain microvascullar endothelial cell, and the model was applied to study the permeability of NGF liposomes. The distribution of NGF of each group was studied by 125I labeled and SDS-PAGE method.

RESULTSThe highest encapsulation proportion was 34%, and the mean size of NGF liposomes was below 100 nm. The permeability of NGF liposomes on in vitro BBB model showed that the liposome could promote NGF to transport across the BBB, the permeability of NGF-SSL-T was the highest. The distribution in the brain showed in an order of NGF concentration NGF-SSL-T > NGF-SSL + RMP-7 > NGF-SSL > NGF-L. There was a close relationship between P(e) (permeability coefficient on in vitro BBB model) and BUI (brain uptake constant in vivo).

CONCLUSIONLiposomes can promote NGF to transport across the BBB, and the transporting ability BBB of NGF-SSL-T which RMP-7 incorporated into the surface of NGF liposomes is the best.

Animals ; Biological Transport ; drug effects ; Blood-Brain Barrier ; Bradykinin ; analogs & derivatives ; pharmacology ; Brain ; metabolism ; Cell Membrane Permeability ; Drug Delivery Systems ; Endothelial Cells ; cytology ; Liposomes ; Male ; Mice ; Nerve Growth Factor ; administration & dosage ; pharmacokinetics ; Particle Size ; Rats ; Tissue Distribution

OBJECTIVETo confirmed reliability and feasibility of intranasal nerve growth factor (NGF) bypassing the blood-brain barrier and its potential neuroprotective effects on acute cerebral ischemia.

METHODS(1) To assay NGF concentrations in different brain regions after middle cerebral artery occlusion (MCAO). Rats were randomly divided into intranasal (i.n.) NGF, intravenous (i.v.) NGF, and untreated group (n = 4). The concentrations of NGF of different brain regions in the three groups after MCAO were measured by ELISA. (2) To observe neuroprotective action of NGF on focal cerebral ischemic damage. Rats were randomly assigned to 4 groups: i.n. vehicle, i.n. NGF, i.v. vehicle, i.v. NGF (n = 8). Treatment was initiated 30 minutes after onset of MCAO and given again 24 hours later. Three neurologic behavioral tests were performed 24 and 48 hours following onset of MCAO. Corrected infarct volumes were determined 48 hours after onset of MCAO.

RESULTSThe olfactory bulb in i.n. NGF group obtained the highest concentration (3252 pg/g) of NGF among all regions, followed by the hippocampus. The NGF concentrations in the olfactory bulb and hippocampus in i.n. NGF group were markedly higher than that in i.v. NGF and control groups. The infarct volume in i.n. NGF group was markedly reduced by 38.8% compared with i.n. vehicle group. I.n. NGF group vestibulum function markedly improved compared with i.n. vehicle group at 24 and 48 hours after onset of MCAO (P24h = 0.02 and P48h = 0.04, respectively).

CONCLUSIONIntranasal NGF could pass through the blood-brain barrier, reach the central nervous system, reduce infarct volume, and improve neurologic function in rats following MCAO. Intranasal delivery of NGF may be a promising treatment for stroke.

Administration, Intranasal ; Animals ; Behavior, Animal ; drug effects ; Blood-Brain Barrier ; Brain ; metabolism ; pathology ; Hippocampus ; metabolism ; Infarction, Middle Cerebral Artery ; metabolism ; pathology ; Injections, Intravenous ; Male ; Nerve Growth Factor ; metabolism ; pharmacology ; Neuroprotective Agents ; pharmacology ; Olfactory Bulb ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Blood brain barrier disruption (BBBD)increases therapeutic agents delivery to brain diseases.Increasing the delivery of therapeutic drugs to the brainimproves out come f or patients with brain tumors.Cervical sympathetic chain block can increase the degree of mannitol induced blood brain barrier disruption in rats.Anesthetic agents may modify hyperosmolar blood brain barrier disruption.Therefore we evaluated the effecfs of pentobarbital and propofol on mannitol induced blood brain barrier disruption(BBBD)in cervical sympathetic nerve blocked rats. METHODS: 14 male Sprague-Dawley rats were divided into 2 groups.Intravenous pentobarbital (group 1,n=7)and propofol (group 2,n=7)were administrated.Rats was blocked with 0.5% bupivacaine on right cervical sympathetic chain.All rats received 37degrees C,25%mannitol (1.75 g/kg) via right carotid artery.BBBD was estimated by Evans blue staining in cerebral hemisphere. RESULTS: Both groups showed BBBD in right side hemisphere and there was no significant difference between group 1 and group 2 in right side hemisphere. CONCLUSIONS: The results suggest that propofol could be used to be anesthetics for BBBD in cervical sympathetic blocked rats.
Anesthetics ; Animals ; Autonomic Nerve Block* ; Blood-Brain Barrier* ; Brain ; Bupivacaine ; Cerebrum ; Evans Blue ; Humans ; Male ; Mannitol* ; Pentobarbital ; Propofol* ; Rats* ; Rats, Sprague-Dawley

BACKGOUND: The barrier can be altered by a number of insults to the brain (e.g., hypertension, freezing, trauma, drug). But the effect of the blood brain barrier distruction immediately after the neural change is unknown. In the present study, we focused on the BBBD after cervical sympathetic chain block. METHODS: 13 male Sprague-Dawley rats were divided into 2 groups. Group 1 (N=7) was blocked with 0.5% bupivacaine on the right cervical sympathetic chain and group 2 (N=6) was blocked with 0.5% bupivacaine on the bilateral cervical sympathetic chain. All rats received 37degrees C, 25% mannitol (1.75 g/kg) via right carotid artery and then, the effect of cervical sympathetic chain block on blood-brain barrier disruption of four cerebral compartment using 99mTc-human serum albumin and Evans blue was evaluated. RESULTS: Both groups showed blood-brain barrier disruption and there was no significant difference between group 1 and group 2 in the anterior and posterior hemisphere of the right side brain. But group 2 showed significant blood-brain barrier disruption than group 1 in anterior and posterior hemisphere of the left brain (p<0.01). CONCLUSIONS: This results suggest that cervical sympathetic chain block can increase the degree of mannitol-induced blood-brain barrier disruption via neural arch or blood flow change.
Anesthetics ; Animals ; Autonomic Nerve Block* ; Blood-Brain Barrier* ; Brain ; Bupivacaine ; Carotid Arteries ; Evans Blue ; Freezing ; Humans ; Hypertension ; Male ; Mannitol* ; Rats* ; Rats, Sprague-Dawley ; Technetium Tc 99m Aggregated Albumin