Vanadium administration ameliorates cortical structural and functional changes in juvenile hydrocephalic mice.

Vanadium is a prevalent neurotoxic transition metal with therapeutic potentials in some neurological conditions. Hydrocephalus poses a major clinical burden in neurological practice in Africa. Its primary treatment (shunting) has complications, including infection and blockage; alternative drug-based therapies are therefore necessary. This study investigates the function and cytoarchitecture of motor and cerebellar cortices in juvenile hydrocephalic mice following treatment with varying doses of vanadium. Fifty juvenile mice were allocated into five groups (n = 10 each): controls, hydrocephalus-only, low- (0.15 mg/kg), moderate- (0.3 mg/kg), and high- (3.0 mg/kg) dose vanadium groups. Hydrocephalus was induced by the intracisternal injection of kaolin and sodium metavanadate administered by intraperitoneal injection 72hourly for 28 days. Neurobehavioral tests: open field, hanging wire, and pole tests, were carried out to assess locomotion, muscular strength, and motor coordination, respectively. The cerebral motor and the cerebellar cortices were processed for cresyl violet staining and immunohistochemistry for neurons (NeuN) and astrocytes (glial fibrillary acidic protein). Hydrocephalic mice exhibited body weight loss and behavioral deficits. Horizontal and vertical movements and latency to fall from hanging wire were significantly reduced, while latency to turn and descend the pole were prolonged in hydrocephalic mice, suggesting impaired motor ability; this was improved in vanadium-treated mice. Increased neuronal count, pyknotic cells, neurodegeneration and reactive astrogliosis were observed in the hydrocephalic mice. These were mostly mitigated in the vanadium-treated mice, except in the high-dose group where astrogliosis persisted. These results demonstrate a neuroprotective potential of vanadium administration in hydrocephalus. The molecular basis of these effects needs further exploration.

A Paternal Methylation Error in the Congenital Hydrocephalic Texas (H-Tx) Rat Is Partially Rescued with Natural Folate Supplements.

Folate deficiencies, folate imbalance and associated abnormal methylation are associated with birth defects, developmental delays, neurological conditions and diseases. In the hydrocephalic Texas (H-Tx) rat, 10-formyl tetrahydrofolate dehydrogenase (FDH) is reduced or absent from the CSF and the nuclei of cells in the brain and liver and this is correlated with decreased DNA methylation. In the present study, we tested whether impaired folate metabolism or methylation exists in sexually mature, unaffected H-Tx rats, which may explain the propagation of hydrocephalus in their offspring. We compared normal Sprague Dawley (SD, n = 6) rats with untreated H-Tx (uH-Tx, n = 6 and folate-treated H-Tx (TrH-Tx, n = 4). Structural abnormalities were observed in the testis of uH-Tx rats, with decreased methylation, increased demethylation, and cell death, particularly of sperm. FDH and FRα protein expression was increased in uH-Tx males but not in folate-treated males but tissue folate levels were unchanged. 5-Methylcytosine was significantly reduced in untreated and partially restored in treated individuals, while 5-hydroxymethylcytosine was not significantly changed. Similarly, a decrease in DNA-methyltransferase-1 expression in uH-Tx rats was partially reversed with treatment. The data expose a significant germline methylation error in unaffected adult male H-Tx rats from which hydrocephalic offspring are obtained. Reduced methylation in the testis and sperm was partially recovered by treatment with folate supplements leading us to conclude that this neurological disorder may not be completely eradicated by maternal supplementation alone.

Study of Compound Sanqi Nanoparticles for Local Infection of Hydrocephalus Patients after Neurosurgery Medium Craniocerebral Injury.

Panax notoginseng is the dried root and rhizome of Panax notoginseng, which has the effect of lowering blood lipid, lowering blood pressure and promoting blood circulation to remove blood stasis. At present, the research on Panax notoginseng is mainly focused on its pharmacological action and its compound preparation, but the research on the granule of Panax notoginseng is less. This paper mainly studied the clinical study of compound notoginseng nanoparticles in the treatment of local infection in patients with hydrocephalus after medium craniocerebral injury in neurosurgery. The purpose of this article is to investigate the effects of compound notoginseng nanoparticles on serum TNF-α, IL-2 and IL-6 in rats with craniocerebral injury and to verify the protective effect of compound notoginseng nanoparticles on the body after craniocerebral injury. In this paper, 90 patients admitted to a hospital in this city were divided into a control group, model group and compound notoginseng nanoparticle group. According to the Zealonga method, the neurological function deficit score of experimental rats in each group was evaluated. The levels of TNF-α, IL-2 and IL-6 in the serum of the three groups were observed 1, 3 and 5 days after treatment. RESULTS: Compared with serum TNF-α, IL-2 and IL-6 of the three groups, there were significant differences in the main effects of time and intervention (P < 0.05). CONCLUSIONS: Compound notoginseng nanoparticles can reduce the contents of TNF-α and IL-6 in serum and increase the expression of IL-2 in rats with craniocerebral injury.

Icariside II Attenuates Chronic Hydrocephalus in an Experimental Subarachnoid Hemorrhage Rat Model.

Purpose To investigate the role of ICA II in subarachnoid hemorrhage (SAH)-  related chronic hydrocephalus. Methods A two hemorrhage injection model of SAH was created in Sprague Dawley rats (6-8 weeks). A total of 125 rats were randomly assigned into five groups: Sham group, SAH group, SAH+ ICA II (1 mg/kg) group, SAH + ICA II (5 mg/kg) group, and SAH + ICA II (10 mg/kg) group. TGF-ß1, phospho-Smad2/3, connective tissue growth factor (CTGF), and procollagen type I carboxy-terminal propeptide (PICP) were assessed via real-time PCR, Western blotting, and enzyme-linked immunosorbent assay. Lateral ventricular index, Masson staining, and Morris water maze tests were employed to evaluate subarachnoid fibrosis, hydrocephalus, and long term neurological function following SAH. Results ICA II (1, 5, 10 mg/kg) inhibited subarachnoid fibrosis, attenuated ventriculomegaly, and effectively suppressed SAH related chronic hydrocephalus. In addition, parallel reduced expression of members of the TGF-ß1/Smad/CTGF signaling pathway were observed. Importantly, ICA II may improve long term neurocognitive deficits after SAH. Conclusion ICA II might suppress fibrosis via inhibition of TGF-ß1/Smad/CTGF pathway, prevent the development of SAH related chronic hydrocephalus, and improve long term neurocognitive defects following SAH.

Herbal medicine for hemorrhage-related hydrocephalus: A systematic review of randomised controlled trials.

BACKGROUND & OBJECTIVE: Hemorrhage related hydrocephalus is a common complication intraventricular hemorrhage, subarachnoid hemorrhage, intracranial hemorrhage and traumatic brain injury. It increases morbidity and disability. The aim of this review is to assess the efficacy of herbal medicine for hemorrhage related hydrocephalus. METHODS: We searched randomized controlled trials (RCTs) investigating herbal medicine through 13 electronic databases. Extracting and assessing the data were performed independently by two authors. The Cochrane risk of bias tool was used to assess the risk of bias. RESULTS: We identified 15 trials investing 12 different herbal formulas. The methodological quality was generally low. In the 11 RCTs of comparisons with conventional treatment alone, herbal medicine plus conventional treatment showed a significant improvement on ventriculomegaly after treatment. Also, the 12 RCTs showed a significant difference on clinical signs and symptoms between two groups. We pooled the data of five trials compared Zhongfengxingnao liquid and Salviae Miltiorrhizae Radix plus conservative treatment with conservative treatment. There were significant effects on normalizing ventricle volume (Huckman index, RR 2.49; 95% CI 1.24-5.00, n = 80) and improving of Chinese scale of clinical neurologic deficit (MD -8.07; 95% CI -9.40 to -6.75, n = 264). CONCLUSION: Herbal medicine has potential benefits on improving ventriculomegaly and clinical signs and symptoms. However, a relatively small participants number and methodological limitations reduced the strength of the evidence. More rigorous trials are warranted.

Nimodipine treatment does not benefit juvenile ferrets with kaolin-induced hydrocephalus.

Prior research on 3-week hydrocephalic rats showed that behavioral deficits and white matter damage could be reduced by treatment with Ca2+ channel blocker nimodipine. We hypothesized that treatment with nimodipine would be also beneficial to young ferrets with kaolin-induced hydrocephalus. Hydrocephalus was induced at 14 days of age and animals were treated either with vehicle, low dose nimodipine (3.2 mg/kg/day), or high dose nimodipine (16 mg/kg/day) for 2 weeks from 38 to 52 days age. Hydrocephalic ferrets developed progressive ventriculomegaly, behavioral changes, and in some cases cortical blindness. These changes were not ameliorated by nimodipine. Histological examination showed damage in periventricular white matter, corpus callosum thinning, axonal damage, reactive astroglial changes, and suppressed cell proliferation compared to non-hydrocephalic controls. Treatment with nimodipine was not beneficial for any of the pathological changes mentioned above; only low dose nimodipine treatment was associated with normalized content of glial fibrillary acidic protein, despite larger ventricles. We conclude that young hydrocephalic ferrets experience behavioral impairments and structural brain damage that are not consistently improved by intermittent nimodipine treatment. Continuous delivery should be considered in further preclinical studies.

Coccidioidal Meningitis: A Review on Diagnosis, Treatment, and Management of Complications.

PURPOSE OF REVIEW: This article summarizes the diagnosis and treatment of coccidioidal meningitis (CM) and its complications. An overview of current and prospective pharmacologic treatment options and monitoring parameters is provided. A consensus has not been reached regarding universally accepted therapeutic serum levels for azoles because of insufficient evidence. We describe the preferred therapeutic drug level ranges that our institution uses to monitor azole therapy. RECENT FINDINGS: Ho et al. described the preparation and administration of intrathecally delivered amphotericin B deoxycholate. Thompson et al. described possible benefits of controversial adjuvant corticosteroid therapy for secondary prevention of vasculitic infarction secondary to CM. CM was universally fatal until the advent of intrathecal amphotericin B deoxycholate therapy, the introduction of which changed the natural history of the disease in much the same way as penicillin changed the natural history of bacterial meningitis. Although there was still significant morbidity, survival rates drastically increased to approximately 70%. The introduction of azole therapy has decreased the side effects and burden of treatment but without a significant change in CM-related mortality and morbidity compared with the use of intrathecal amphotericin B deoxycholate therapy.

Magnesium sulfate therapy is of mild benefit to young rats with kaolin-induced hydrocephalus.

Hydrocephalus causes damage to periventricular white matter at least in part through chronic ischemia. Magnesium sulfate (MgSO4) has been shown to be protective in various models of neurologic injury. We hypothesized that this agent would ameliorate the effects of experimental childhood-onset hydrocephalus. Hydrocephalus was induced in 3- and 4-wk-old rats by injection of kaolin into the cisterna magna. Tests of cognitive and motor function were performed on a weekly basis. In a blinded and randomized manner, MgSO4 was administered in two separate experiments (s.c. injection 0.85, 4.1, or 8.2 mM/kg/d), supplemented by osmotic minipump infusion (0.03 mM/d) to prevent low trough levels for 2 wk, beginning 2 wk after induction of hydrocephalus. The brains were then subjected to histopathological and biochemical analyses. With the 4.1 mM/kg/d dose, serum Mg++ levels were elevated transiently from 1.3 to approximately 7 mM/L. We observed statistically significant improvement in gait performance and reduced astroglial reaction. There was also a trend to improved memory performance, but no evidence of increased myelin or synaptic protein content. The 8.2 mM/kg/d dose was associated with sedation and there was no evidence of improvement in any parameter. We conclude that MgSO4 might be mildly protective in experimental hydrocephalus.

Use of acetazolamide to decrease cerebrospinal fluid production in chronically ventilated patients with ventriculopleural shunts.

Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease cerebrospinal fluid (CSF) production in both in vivo and in vitro animal models. We report two children with hydrocephalus who experienced multiple shunt failures, and who had externalised ventriculostomy drains (EVD) prior to ventriculopleural shunt placement. The effects of increasing doses of ACTZ on CSF production and subsequent tolerance to ventriculopleural shunts were evaluated. The patients had a 48% and a 39% decrease in their EVD CSF output when compared to baseline with maximum ACTZ dose of 75 mg/kg/day and 50 mg/kg/day, respectively (p < 0.05). This is the first report of change in CSF volume in children after extended treatment with ACTZ. ACTZ treatment in mechanically ventilated paediatric patients with hydrocephalus may improve tolerance of ventriculopleural shunts and minimise respiratory compromise. Potassium and bicarbonate supplements are required to correct metabolic disturbances.