OBJECTIVE: On the magnetic resonance image (MRI) of the infiltrating brain tumor, enhancement is usually higher in malignant tumor than in benign tumor, and tumor cells can invade into the peritumoral area without definite enhancement. In various pathological conditions, the blood brain barrier (BBB) becomes changed to pathological condition, allowing various materials extravasating into the interstitial space, and degree of enhancement is depend on the pathology. Authors performed dynamic MRI on enhancing and surrounding edematous area in order to evaluate the degrees of opening of BBB, to differentiate tumor from non-tumorous condition, and to determine its relationship with the recurrence of the tumor. METHODS: Dynamic MRI was performed in 25 patients. Dynamic scans were done every 15 seconds after administration of Gd-DTPA on the enhancing and surrounding area for maximum 300 seconds, and the patterns of enhancement were analysed. The enhancement curve with initial steep increase followed by slow decrease was defined as "N pattern", those with initial steep increase followed by additional slow increase as "T pattern", and those with initial steep increase followed by plateau as "E pattern". Histopathological findings were compared with the dynamic scan. RESULTS: The graphs taken from enhancing area showed "T pattern" regardless of pathology. In the surrounding area, "T pattern" was noticed in the malignant tumors, but "E pattern" or "N pattern" was noted in low-grade or benign tumors and non-tumorous condition. "T pattern" in the surrounding area was related to the malignancy with tumor cell infiltration and recurrence. CONCLUSION: The results suggest that the malignant tumor infiltration changes the condition of BBB enough to extravasate the Gd-DTPA. Enhancement pattern in the surrounding edematous area may be a useful information to differentiate the malignant glioma with the low-grade and benign tumors or other non-tumorous conditions.
Blood-Brain Barrier ; Brain Neoplasms* ; Brain* ; Gadolinium DTPA ; Glioblastoma ; Glioma ; Humans ; Magnetic Resonance Imaging* ; Pathology ; Recurrence

The authors compared the changes of morphology, blood brain barrier alteration, pathology, arterial blood lactate content and cerebrospinal fluid lactate content between an intermittent brain retraction group and a continuous brain retraction group in 56 mongrel cats. The results were as follows ; 1) Microscopically, hemorrhages were punctate in 15 cases among 25 cases in the intermittent retraction group. However, there were multiple or large hemorrhages in 13 cases among the 25 cases in the continuous brain retraction group. 2) All cases of the intermittent retraction group showed 0~25% Evans blue staining of the coronal section crossing the retraction site. However, 8 cases among the 25 cases of the continuous retraction group showed 51~75% Evans blue staining and 4 cases of this group showed 76~100% staining. 3) With photomicroscopy, the authors noted small hemorrhage and cellular swelling in the intermittent retraction group instead of pyknosis, hemorrhagic necrosis, vacuolation in the continuous retraction group. 4) The change of arterial blood lactate content was from 1.22+/-0.24mmol/L at preretraction time to 1.42+/-0.26mmol/L at 90 minutes after release of retractor in the intermittent retraction group(p<0.01). In the continuous retraction group, the authors noted a change in the lactate content from 1.20+/-0.38mmol/L to 3.15+/-0.97mmol/L for the same time as above(p<0.001). 5) The change of CSF lactate content in the intermittent retraction group was from 1.39+/-0.29mmol/L at preretraction time to 1.43+/-0.23mmol/L at 90 minutes after release of retractor(p>0.05). In the continuous retraction group, this author noted change in the lactate content from 1.37+/-0.28mmol/L to 2.11+/-0.52mmol/L for the same time as described above(p<0.01). From the above results, the superiority of the intermittent brain retraction was demonstrated as compared with the continuous brain retraction. Also the possible utilization of this experimental method was discussed for other wxperimental studies on ischemia.
Animals ; Blood-Brain Barrier ; Brain* ; Cats* ; Cerebrospinal Fluid ; Evans Blue ; Hemorrhage ; Ischemia ; Lactic Acid ; Necrosis ; Pathology

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*

OBJECTIVETo investigate the influence of therapeutic bloodletting at Jing-well points and hypothermia on acute cerebral edema after traumatic brain injury (TBI) in rats.

METHODSSeventy-five SD rats were randomly divided into sham-operation group (Sham), TBI group (TBI), bloodletting group (BL), mild-induced hypothermia group (MIH), and bloodletting plus MIH group (BL + MIH) (n = 15). The model of TBI was established by electric controlled cortical impactor (eCCI). The rats of BL group were bloodletting at Jing-well points immediately after injury, twice daily. While the MIH group was settled on a hypothermia blanket promptly after TBI for 6 hours, so that the temperature dropped to 32 degrees. Each of measurement was performed after 48 hours. Magnetic resonance imaging (MRI) was used to evaluate the dynamic impairment of cerebral edema after TBI (n = 3). In addition, mNSS score, measurements of wet and dry brain weight, and Evans Blue assay were performed to investigate the neurologic deficit, cerebral water content (n = 8), and blood-brain barrier permeability (BBB), (n = 4), respectively.

RESULTSMRI analysis showed that the cerebral edema, hematoma and midline shifting of rats in TBI group was more serious than other treatment group. Meanwhile compared with TBI group, the mNSS scores of every treatment group were meaningfully lower (all P < 0.05). Furthermore, treatment with BL+ MIH group was superior to the separated BL and MIH group (all P < 0.01). In addition, brain water content of each intervention group reduced to varying degrees (all P < 0.05), especially that of MIH group and BL + MIH group (P <0.01). BBB permeability of each treatment group was also significantly improved (all P < 0.01), and the improvement in MIH group and BL + MIH group was much better than the BL alone group (P < 0.05, P < 0.01).

CONCLUSIONOur major finding is that bloodletting at Jing-well points and MIH can reduce cerebral edema and BBB dysfunction and exert neuroprotective effects after TBI. The results suggest that the combination of BL and MIH is more effective than other treatment being used alone.

Animals ; Blood-Brain Barrier ; Bloodletting ; Brain ; pathology ; Brain Edema ; prevention & control ; Brain Injuries ; therapy ; Hypothermia, Induced ; Rats ; Rats, Sprague-Dawley

Accumulated evidence suggests that sporadic cases of Alzheimer's disease (AD) make up more than 95% of total AD patients, and diabetes has been implicated as a strong risk factor for the development of AD. Diabetes shares pathological features of AD, such as impaired insulin signaling, increased oxidative stress, increased amyloid-beta (Aβ) production, tauopathy and cerebrovascular complication. Due to shared pathologies between the two diseases, anti-diabetic drugs may be a suitable therapeutic option for AD treatment. In this article, we will discuss the well-known pathologies of AD, including Aβ plaques and tau tangles, as well as other mechanisms shared in AD and diabetes including reactive glia and the breakdown of blood brain barrier in order to evaluate the presence of any potential, indirect or direct links of pre-diabetic conditions to AD pathology. In addition, clinical evidence of high incidence of diabetic patients to the development of AD are described together with application of anti-diabetic medications to AD patients.
Alzheimer Disease ; Blood-Brain Barrier ; Encephalitis ; Humans ; Incidence ; Insulin ; Neuroglia ; Oxidative Stress ; Pathology ; Risk Factors ; Tauopathies

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by loss of dopaminergic (DA) neurons in the dense part of the substantia nigra (SNpc). Postmortem analysis of PD patients and experimental animal studies found that microglial cell activation and increased levels of pro-inflammatory factors were common features of PD brain tissue. At the same time, the invasion and accumulation of peripheric immune cells were detected in the brain of PD patients. In this paper, peripheral inflammation across the blood-brain barrier (BBB), the misfolded α-synuclein (α-syn)-induced microglial cell activation and intracerebral inflammation in PD are summarized, providing potential therapeutic measures for delaying the onset of PD.
Animals ; Blood-Brain Barrier ; Dopaminergic Neurons ; pathology ; Humans ; Inflammation ; pathology ; Microglia ; Parkinson Disease ; pathology ; Substantia Nigra ; pathology ; alpha-Synuclein

OBJECTIVETo evaluate the role of water channel AQP4 in NMDA-induced brain injury in mice.

METHODSIn AQP4 gene knockout (AQP4(-/-)) mice, brain injury was induced by microinjection of NMDA into the cortex. The injured area was determined by toluidine blue staining, degenerated neurons were detected by Fluro-Jade B staining, and increased blood-brain barrier (BBB) permeability was evaluated by IgG immunostaining.

RESULTCompared with wild-type mice, AQP4(-/-) mice exhibited increased cortical lesion area, aggravated neuron degeneration, and increased BBB disruption after NMDA microinjection.

CONCLUSIONAQP4 may play a protective role in NMDA-induced brain injury in mice.

Animals ; Aquaporin 4 ; genetics ; physiology ; Blood-Brain Barrier ; pathology ; Brain ; drug effects ; pathology ; Mice ; Mice, Knockout ; N-Methylaspartate ; toxicity

OBJECTIVETo establish a method for detecting circulating brain microvascular endothelial cells (cBMECs), a novel biomarker of blood-brain barrier (BBB) injury.

METHODSBlood samples were collected from 33 patients with AIDS encephalitis and 13 healthy subjects for detection of cBMECs, cECs and EPCs using magnetic affinity isolation and immune identification technology.

RESULTSThe numbers of cBMECs, cECs and EPCs were significantly higher in the AIDS patients than in the control subjects (t=4.298, P<0.01; t=4.886, P<0.01; t=4.889, P<0.01). An significant association was also noted between HIV load and cBMEC number (r=0.928, P<0.01).

CONCLUSIONWe have successfully established a method for detecting peripheral blood cBMECs, which can be of important value in non-invasive assessment of BBB injury.

Acquired Immunodeficiency Syndrome ; physiopathology ; Biomarkers ; Blood-Brain Barrier ; pathology ; Cell Separation ; methods ; Cells, Cultured ; Endothelial Progenitor Cells ; cytology ; Humans

OBJECTIVEThe investigated the effects of Dengzhan Xixin on brain water content, blood-brain barrier (BBB) permeability, T2-weighted imaging (T2WI), metabolites and the lesion ratio after cerebral ischemia-reperfusion injuries (IRI).

METHODThe 65 rats were randomly individed into three groups, the sham-operated group, the ischemia-reperfusion group and the Dengzhan Xixin treatment group. The models of ischemia-reperfusion of middle cerebral artery in rats were established by placing an intraluminal suture. The Dengzhan Xixin treatment group were injected 10% Dengzhan Xixin injection 22.5 mg kg(-1) after ischemia 1.5 h. The sh am-operated group (n=5) were sacrificed on 1 to measure brain water content and BBB permeability. The rats of the ischemia-reperfusion group (n=30) and the Dengzhan Xixin treatment group (n=30) were sacrificed at reperfusion for 6 h, 12 h, 1 d, 2 d, 4 d, 7 d, respectively, after ischemia 1.5 h. The additional 35 rats were individed into the same three groups. The changes of T2WI and metabolites in the brain were observed, and rats were sacrificed at reperfusion for 1 d, 2 d, 4 d after ischemia 1.5 h to determine the lesion ratio by TTC.

RESULTIn the ischemia-reperfusion group, brain water content(77.93+/-0.68)% and BBB permeability (3.77+/-0.28) increased after reperfusion for 6 h. The peak time of brain water content was at 4 d (83.82+/-0.49)% and BBB permeability was at 2 d (5.51+/-0.24)%. In the ischemia-reperfusion group and the Dengzhan Xixin treatment group, there were hyperintense signals in the injury region of T2WI. In the ischemia-reperfusion group after reperfusion for 1 d, the ratio of NAA/Cr decreased and Cho/Cr increased. In the Dengzhan Xixin treatment group, the ratio of NAA/Cr increased and Cho/Cr decreased. In the treatment group, the lesion ratio decreased by TTC was 16.78+/-1.45 and in the ischemia-reperfusion group was 21.27+/-1.73 at 2 d.

CONCLUSIONDengzhan Xixin may relieve cerebral ischemia-reperfusion injury by influencing the metabolites of brain, stabilizing BBB and decreasing brain edema.

Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain Ischemia ; complications ; metabolism ; pathology ; Flavonoids ; pharmacology ; Male ; Permeability ; drug effects ; Rats ; Rats, Wistar ; Reperfusion Injury ; complications ; metabolism ; pathology ; Water ; metabolism

OBJECTIVETo investigate the impact of intrauterine infection induced by LPS injection on long-term brain development of premature rats.

METHODSEighteen day-gestation pregnant rats were randomly assigned to a control group receiving an intraperitoneal injection of normal saline, and two infection groups that were intraperitoneally injected with 0.3 mg/kg or 0.6 mg/kg LPS. Twenty-four hours after injection, 7 pregnant rats of each group were sacrificed. The pathological changes of the placenta after hematoxylin and eosin staining were observed under a light microscope. The neural cell apoptosis of fetal brains was examined by the TUNEL assay. The remained pregnant rats were induced to labour before 21 gestation days. The long-term brain development of premature rats was tested with the Y type electric maze on postnatal day 42.

RESULTSObvious pathological changes were observed in the placenta in the infection groups. The apoptotic neural cells in the fetal brain increased in the infection groups compared with that in the control group (32.41+/-5.36 in the 0.3 mg/kg infection group and 66.41+/-7.61 in the 0.6 mg/kg infection group vs 8.00+/-0.36 in the control group; P<0.01). The number of trials to criterion in the Y type maze test in the infection groups was much more than that in the control group [117.8+/-8.7 (0.3 mg/kg infection group) and 194.4+/-13.7 (0.6 mg/kg infection group) vs 56.8+/-3.7 (control group); P<0.01]. The number of correct reactions in memory retaining in the infection groups was lower than that in the control group (0.62+/-0.09 in the 0.3 mg/kg infection group and 0.37+/-0.09 in the 0.6 mg/kg infection group vs 0.92+/-0.06 in the control group; P<0.05).

CONCLUSIONSIntrauterine infection can cause fetal rats' neural cell apoptosis and affect adversely long-term brain development of neonatal rats.

Animals ; Apoptosis ; Bacterial Infections ; physiopathology ; Blood-Brain Barrier ; Brain ; growth & development ; pathology ; Female ; Maze Learning ; Neurons ; pathology ; Pregnancy ; Pregnancy Complications, Infectious ; physiopathology ; Rats ; Rats, Wistar ; Uterus ; microbiology