X. F. Yang

Effects of selective brain cooling in patients with severe traumatic brain injury: a preliminary study.

We prospectively investigated noninvasive selective brain cooling (SBC) in patients with severe traumatic brain injury. Sixty-six in-patients were randomized into three groups. In one group, brain temperature was maintained at 33-35 °C by cooling the head and neck (SBC);in a second group, mild systemic hypothermia (MSH; rectal temperature 33-35°C) was produced with a cooling blanket; and a control group was not exposed to hypothermia. Natural re-warming began after 3 days. Mean intracranial pressure 24, 48 or 72 h after injury was significantly lower in the SBC group than in the control group. Mean serum superoxide dismutase levels on Days 3 and 7 after injury in the SBC and MSH groups were significantly higher than in the control group. The percentage of patients with a good neurological outcome 2 years after injury was 72.7%, 57.1% and 34.8% in the SBC, MSH and control groups, respectively. Complications were managed without severe sequelae. Non-invasive SBC was safe and effective.

Apocynin Attenuates Cerebral Infarction after Transient Focal Ischaemia in Rats

This study investigated whether inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase attenuates cerebral infarction after transient focal ischaemia in rats. Focal ischaemia (1.5 h) was produced in male Sprague-Dawley rats (250 − 280 g) by middle cerebral artery occlusion. Some rats also received treatment with 50 mg/kg apocynin, a NADPH oxidase inhibitor, by intraperitoneal injection 30 min prior to reperfusion. Two hours after reperfusion, brains were harvested to measure NADPH oxidase activity and superoxide levels. After 24 h, the remaining brains were harvested to investigate infarct size. NADPH oxidase activity and superoxide level were all augmented 2 h after reperfusion compared with controls. Apocynin treatment significantly reduced NADPH oxidase activity and superoxide levels. Cerebral infarct size was significantly smaller in the apocynin-treated group compared with those undergoing ischaemia/reperfusion alone. These results indicate that inhibition of NADPH oxidase attenuates cerebral infarction after transient focal ischaemia in rats, suggesting that inhibition of NADPH oxidase may provide a therapeutic strategy for ischaemic stroke.

Overexpression of vascular endothelial growth factor (VEGF) receptors on keratinocytes in psoriasis: regulated by calcium independent of VEGF.

Psoriasis is a common chronic inflammatory disease of the skin characterized by epidermal hyperplasia and angiogenesis. Recently, vascular endothelial growth factor receptors (VEGFRs, including VEGFR‐1, VEGFR‐2 and VEGFR‐3) were found to be expressed in normal human epidermis and associated with proliferation and migration of keratinocytes. The purpose of this study is to investigate the expression of VEGFRs on psoriatic keratinocytes and the roles of calcium and VEGF in regulating VEGFR expression. Skin samples from 17 patients with chronic plaque psoriasis and 11 normal controls were included. The expression of VEGFRs in psoriatic keratinocytes at mRNA and protein levels was determined by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Western blot analysis. Localization of the VEGFRs in skin lesions was determined by immuno‐fluorescent method. Since keratinocyte proliferation and differentiation rely on calcium concentrations, and VEGF is overexpressed in psoriatic epidermis, we further investigated the roles of calcium and VEGF in regulating the expression of VEGFRs. Overexpression of VEGFR‐1, VEGFR‐2 and VEGFR‐3 in psoriatic epidermis was demonstrated both at mRNA and protein levels in vitro. VEGFRs were strongly labeled in non‐lesional, perilesional and lesional psoriatic keratinocytes in all viable epidermal stratums in vivo. Furthermore, both exogenous VEGF165 and calcium enhanced the expression of VEGFRs. Calcium also enhanced the expression of VEGF in non‐lesional psoriatic keratinocytes, while targeted blockade of VEGF activity by bevacizum‐ab could not inhibit calcium‐induced up‐regulation of protein levels of VEGFRs. We conclude from these results that VEGFRs are overexpressed in lesional psoriatic epidermal keratinocytes. Both calcium and VEGF regulate VEGFRs expression in psoriatic epidermis. More importantly, calcium is a potential regulator for VEGFR independent of VEGF.

A prospective study of early versus late craniectomy after traumatic brain injury

Background: Decompressive craniectomy is an important method for managing traumatic brain injury (TBI). At present, controversies about this procedure exist, especially about the optimum operative time for patients with TBI. Methods: A prospective study was performed at the First Affiliated Hospital, College of Medicine, Zhejiang University. From January 2008 to December 2009, 25 patients who underwent early decompressive craniectomy were included in the study group, and 19 patients who underwent “late” decompressive craniectomy as a second-tier therapy for intracranial hypertension were included as a comparison group. Results: The 30-day mortality after the operation was 16% in the study group. The overall mortality rate was 20% at the 6-month follow-up. A total of 52% of the patients (13 patients) had good outcomes, and 7 patients remained in a severely disabled or vegetative state. In the comparison group, 4 patients died, and 12 had good outcomes at the 6-month follow-up. The remaining 3 patients had poor outcomes. The study group was well matched with the comparison group. However, the outcomes in the study group were not better than those in the comparison group, as evaluated by the 6-month GOS score. Conclusion: Early decompressive craniectomy as a first-tier therapy for intracranial hypertension did not improve patient outcome when compared with “late” decompressive craniectomy for managing TBI.

Cranioplasty for patients developing large cranial defects combined with post-traumatic hydrocephalus after head trauma

Background: Large cranial defects combined with hydrocephalus after decompressive craniectomy are a common, harsh reality among patients with head trauma. Typically, a shunt is first used to relieve the hydrocephalus. However, subsequently the patients may develop a severe sinking scalp flap over the skull defect before cranioplasty, which would make the procedure difficult. Methods: This problem was overcome by temporarily adjusting the shunt pressure using a programmable ventriculoperitoneal shunt tube, which allowed expansion of the depressed scalp flap and facilitated the subsequent cranioplasty. This study describes two patients who were treated for this problem after severe head trauma. Results: When performing a titanium mesh cranioplasty after a shunt, this new method facilitated the separation of the scalp from the underlying muscle or dura and obliterated the dead space between the titanium mesh and the underlying tissue. Both patients had satisfactory outcomes without complications. Conclusions: This method is easy and safe and it facilitates the cranioplasty, reducing the potential complications, including intracranial haematoma, effusions and infection, and thereby improving the patient outcome.

Shunt implantation in a special sub-group of post-traumatic hydrocephalus—patients have normal intracranial pressure without clinical representations of hydrocephalus

Background: Post-traumatic hydrocephalus (PTH) is a frequent complication secondary to traumatic brain injury (TBI) and controversy remains over whether to perform a shunt placement for patients with normal pressure hydrocephalus when the patient is too injured to display symptoms or has atypical symptoms. Method: A hospital-based retrospective study was performed in patients who developed normal pressure hydrocephalus, without atypical symptoms, from January 2004 to June 2007. Information regarding patients’ demographics, TBI, hydrocephalus and outcome was collected. Results: A total of 31 patients were involved in this study. At the 12-month follow-up, 20 patients (64.5%) showed clear improvement. Among the 10 patients who developed PTH after decompressive craniectomy, cranioplasty was performed after shunt implantation and clinical improvement was observed in nine patients. Additionally, in this series, the patients’ age and the severity of hydrocephalus, assessed by CT imaging before shunt placement, significantly correlated with improvement. Conclusion: Although the effect was not definitively established, many patients in the sub-group of PTH patients described here would benefit from shunt placement, especially when they simultaneously have large cranial defects after surgical decompression and underwent cranioplasties after shunt placement. Additionally, younger patients and those with less severe hydrocephalus before shunt placement may expect a better outcome after shunt placement.

VEGF upregulates VEGF receptor-2 on human outer root sheath cells and stimulates proliferation through ERK pathway.

Vascular endothelial growth factor (VEGF) is a key regulator of physiological and pathological angiogenesis. The biological effects of VEGF are mediated by receptor tyrosine kinases. VEGF receptor-2, the primary receptor for VEGF, is thought to mediate most functional effects. In this study, we examined the expression and roles of VEGF receptor-2 on human outer root sheath cells (ORS). The expression of VEGFR-2 was determined at mRNA and protein levels by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Localization of VEGFR-2 in ORS cells was detected by immunofluorescence. The effect of VEGF on ORS cell proliferation was determined by MTT assays. Our data showed the expression of VEGFR-2 on ORS cells at both mRNA and protein levels. Immunostaining for VEGFR-2 demonstrated strong signal on cultured ORS cells. Exogenous VEGF165 stimulated proliferation of ORS cells and upregulated expression of VEGFR-2 in a dose-dependent manner. Moreover, VEGF165 induced phosphorylation of VEGFR-2, PLC-γ1, PKC-α, MEK, and p44/42 MAPK (ERK1/2) in a time-dependent manner. Taken together, human ORS cells express functional VEGF receptor-2 and exogenous VEGF165 upregulates expression of VEGFR-2 and stimulates proliferation of ORS cells via VEGFR-2 mediated ERK signaling pathway.

Subdural effusion secondary to decompressive craniectomy in patients with severe traumatic brain injury

Dear Editor, Firstly, thanks for the attention on our study. Nowadays, decompressive craniectomy is an important method for the management of patients with severe head trauma, and apparently the prevention and management of complications are crucial parts of this surgical method. Actually, a great part of these complications would be secondary to head trauma or craniotomy as well, including subdural effusion, post-traumatic hydrocephalus, intracranial infection, cerebrospinal fluid leakage, intracranial rehemorrhage, and epilepsy. Subdural effusion is a complication that could be secondary to both head trauma and craniotomy. The incidence rate of subdural effusion in head trauma was between 7 and 12% [3], and that after decompressive craniectomy was between 21 and 50% reportedly [1, 2, 4, 5]. In our series, this rate was 21.3%. We agree on the explanation of the reasons for the high incidence of subdural effusion secondary to decompressive craniectomy from Dr. Cumher Kilincer. However, here we want to emphasize another reason for the development of subdural effusion. We have treated a patient who was transferred to our hospital 2 months after surgical decompression for severe head trauma. The local hospital sent him to our hospital for deterioration of consciousness, and the CT scan disclosed subdural effusion contralateral to the decompressive side (Fig. 1). We reviewed the patient’s medical record, and it was found that though the brain edema was not disclosed from the CT on the late phase of head trauma the treatment of dehydration was still lasted. The excessive dehydration was believed to be an important reason for the development of subdural effusion. After stopping the dehydration, this patient recovered under conservative treatment and the CT approved the resolution of effusion. Such a case may not be the only one, and the development

Brain Tumour Stem Cells and Neural Stem Cells: Still Explored by the Same Approach?

Brain tumour stem cells (BTSCs) are chiefly responsible for the in vivo long-term growth and recurrence of malignant gliomas and may be a potential treatment target. They resemble neural stem cells (NSCs), so their self-renewal and differentiation are currently investigated by the same methods used to study NSCs. There are, however, essential differences between these cell types: in many cases the marker expression pattern of BTSCs does not match the CD133+/NSE−/FAP− pattern of NSCs; BTSC tumourigenicity is independent of marker expression; and while attachment, serum-containing medium and withdrawal of mitogens (epidermal growth factor [EGF] and basic fibroblast growth factor [bFGF]) are essential to induce NSCs to differentiate, they do not affect BTSC tumourigenicity. Evidence implies that research on the renewal and differentiation of BTSCs should be orientated towards tumourigenicity and is essentially a pharmaceutical problem. Such an approach may contribute to the development of an accurate definition of BTSCs and to the search for selective differentiation-inducing drugs for BTSCs.

The Presence of Hepatitis B Surface Antigen in the Ova of Pregnant Women and Its Relationship with Intra-Uterine Infection by Hepatitis B Virus

Vertical transmission of hepatitis B virus (HBV) has been proposed to play an important role in mother-to-child transmission, although the extent to which vertical transmission via oocytes contributes to neonatal HBV infection remains unknown. Ovarian biopsies were collected during caesarean sections in 68 clinically asymptomatic pregnant women who were carriers of HBV. The presence of hepatitis B surface antigen (HBsAg) in the ova of pregnant women was determined by immunohistochemistry. Serum markers of HBV infection in pregnant women and their neonates were analysed. It was found that, of 68 women, the ova were positive for HBsAg in only one woman and her neonate was negative for any serum HBV markers 3 days after birth. Of 68 neonates, one was positive for serum HBV markers 3 days after birth and his mothers ova were negative for HBsAg. These findings indicate that vertical transmission via oocytes may not be the major route of HBV intra-uterine infection.