Transcription blockage by DNA damage in nucleotide excision repair-related neurological dysfunctions.

Human genetic syndromes deficient in nucleotide excision repair (NER), such as xeroderma pigmentosum and Cockayne syndrome, may present neurological abnormalities and premature aging symptoms. Unrepaired endogenously generated DNA damage that hampers transcription is a strong candidate that contributes to the development of these severe effects in neuronal tissue. Endogenous lesions include those generated due to byproducts of cellular metabolisms, such as reactive oxygen species. This review presents much of the evidence on the mechanisms related to neurodegenerative processes associated with DNA damage responses. The primary focus is on the effects of the transcription machinery, including the accumulation of DNA•RNA hybrids (R-loops) that, in turn, influence DNA damage and repair metabolism. Moreover, several neuronal tissues present higher expression of long genes, a genomic subset more affected by DNA lesions, which may explain part of the neurological abnormalities in these patients. Also, neuronal tissues have different DNA repair capabilities that might result in different neurological consequences, as observed in patients and NER deficient animal models. The better understanding of how the accumulation of transcription blocking lesions can lead to neurological abnormalities and premature aging-like phenotypes may assist us in finding potential biomarkers and therapeutic targets that might improve the lives of these patients, as well as other neurological disorders in the general population.

Mucinous Degeneration on MRI After Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: Frequency and Association With Clinical Outcomes.

BACKGROUND. Patients with nonmucinous rectal adenocarcinoma may develop mucinous changes after neoadjuvant chemoradiotherapy, which are described as mucinous degeneration. The finding's significance in earlier studies has varied. OBJECTIVE. The purpose of this study was to assess the frequency of mucinous degeneration on MRI after neoadjuvant therapy for rectal adenocarcinoma and to compare outcomes among patients with nonmucinous tumor, mucinous tumor, and mucinous degeneration on MRI. METHODS. This retrospective study included 201 patients (83 women, 118 men; mean age, 61.8 ± 2.2 [SD] years) with rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision from October 2011 to November 2015, underwent baseline and restaging rectal MRI examinations, and had at least 2 years of follow-up. Two radiologists independently evaluated MRI examinations for mucin content, which was defined as T2 hyperintensity in the tumor or tumor bed, and resolved differences by consensus. Patients were classified into three groups on the basis of mucin status: those with nonmucinous tumor (≤ 50% mucin content on baseline and restaging examinations), those with mucinous tumor (> 50% mucin content on baseline and restaging examinations), and those with mucinous degeneration (≤ 50% mucin content on baseline examination and > 50% content on restaging examination). The three groups were compared. RESULTS. Interreader agreement for mucin content, expressed as a kappa coefficient, was 0.893 on baseline MRI and 0.890 on restaging MRI. Of the 201 patients, 156 (77.6%) had nonmucinous tumor, 34 (16.9%) had mucinous tumor, and 11 (5.5%) had mucinous degeneration. Mucin status was not significantly associated with complete pathologic response (p = .41) or local or distant recurrence (both p > .05). The death rate during follow-up was not significantly different (p = .21) between patients with nonmucinous tumor (23.1%), those with mucinous tumor (29.4%), and those with mucinous degeneration (9.1%). In adjusted Cox regression analysis, with mucinous degeneration used as reference, the HR for the overall survival rate for the mucinous tumor group was 4.7 (95% CI, 0.6-38.3; p = .14), and that for the nonmucinous tumor group was 8.0 (95% CI, 0.9-59.9; p = .06). On histopathologic assessment, all 11 patients with mucinous degeneration showed acellular mucin, yet 10 of 11 patients showed viable tumor (i.e., in nonmucinous portions of the tumors). CONCLUSION. Mucinous degeneration on MRI is not significantly associated with pathologic complete response, recurrence, or survival. CLINICAL IMPACT. Mucinous degeneration on MRI is uncommon and should not be deemed an indicator of pathologic complete response.

Clinical and Surgical Approach for Cerebral Cortical Dysplasia.

The present article describes pathophysiological and clinical aspects of congenital malformations of the cerebral tissue (cortex and white matter) that cause epilepsy and very frequently require surgical treatment. A particular emphasis is given to focal cortical dysplasias, the most common pathology among these epilepsy-related malformations. Specific radiological and surgical features are also highlighted, so a thorough overview of cortical dysplasias is provided.

Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells.

UVA-induced mutagenesis was investigated in human pol eta-deficient (XP-V) cells through whole-exome sequencing. In UVA-irradiated cells, the increase in the mutation frequency in deficient cells included a remarkable contribution of C>T transitions, mainly at potential pyrimidine dimer sites. A strong contribution of C>A transversions, potentially due to oxidized bases, was also observed in non-irradiated XP-V cells, indicating that basal mutagenesis caused by oxidative stress may be related to internal tumours in XP-V patients. The low levels of mutations involving T induced by UVA indicate that pol eta is not responsible for correctly replicating T-containing pyrimidine dimers, a phenomenon known as the 'A-rule'. Moreover, the mutation signature profile of UVA-irradiated XP-V cells is highly similar to the human skin cancer profile, revealing how studies involving cells deficient in DNA damage processing may be useful to understand the mechanisms of environmentally induced carcinogenesis.

Phosphorylation of S6 Protein as a Potential Biomarker in Surgically Treated Refractory Epilepsy.

The tuberous sclerosis complex (TSC), focal cortical dysplasia IIB (FCD IIB), and hemimegalencephaly (HME) exhibit similar molecular features that are dependent on the hyperactivation of the mTOR pathway. They are all associated with refractory epilepsy and the need for surgical resection with varying outcomes. The phosphorylated protein S6 (pS6) is a downstream target of mTOR, whose increased expression might indicate mTOR hyperactivation, but which is also present when there is no alteration in the pathway (such as in FCD type I). We have performed immunohistochemical marking and quantification of pS6 in resected brain specimens of 26 patients clinically and histologically diagnosed with TSC, FCD IIB, or HME and compared this data to a control group of 25 patients, to measure the extent of pS6 positivity and its correlation with clinical aspects. Our results suggest that pS6 may serve as a reliable biomarker in epilepsy and that a greater percentage of pS6 marking can relate to more severe forms of mTOR-dependent brain anomalies.

Toxicogenetic and antiproliferative effects of chrysin in urinary bladder cancer cells.

The antitumour activity of chrysin have been studied in several types of cancer cells. In urinary bladder cancer, its cytotoxic effects have already demonstrated; however, its mechanism of action is not completely understood and the role of tumour protein p53 (TP53) gene in these effects is unclear. In this study, we investigated the role of chrysin (10, 20, 40, 60 80 and 100 µM) in progression of bladder tumour cells with different status of the TP53 gene and different degrees of tumour (RT4, grade 1, TP53 wild type; 5637, grade 2, TP53 mutated and T24, grade 3, TP53 mutated). Results demonstrated that chrysin inhibited cell proliferation by increasing reactive oxygen species and DNA damage and inhibited cell migration in all cell lines. In TP53 wild-type cells, a sub-G1 apoptotic population was present. In mutated TP53 cells, chrysin caused arrest at the G2/M phase and morphological changes accompanied by downregulation of PLK1, SRC and HOXB3 genes. In addition, in Grade 2 cells, chrysin induced global DNA hypermethylation and, in the highest-grade cells, downregulated c-MYC, FGFR3 and mTOR gene expression. In conclusion, chrysin has antiproliferative and toxicogenetic activity in bladder tumour cells independently of TP53 status; however, the mechanisms of action are dependent on TP53 status.

Cockayne Syndrome: The many challenges and approaches to understand a multifaceted disease.

The striking and complex phenotype of Cockayne syndrome (CS) patients combines progeria-like features with developmental deficits. Since the establishment of the in vitro culture of skin fibroblasts derived from patients with CS in the 1970s, significant progress has been made in the understanding of the genetic alterations associated with the disease and their impact on molecular, cellular, and organismal functions. In this review, we provide a historic perspective on the research into CS by revisiting seminal papers in this field. We highlighted the great contributions of several researchers in the last decades, ranging from the cloning and characterization of CS genes to the molecular dissection of their roles in DNA repair, transcription, redox processes and metabolism control. We also provide a detailed description of all pathological mutations in genes ERCC6 and ERCC8 reported to date and their impact on CS-related proteins. Finally, we review the contributions (and limitations) of many genetic animal models to the study of CS and how cutting-edge technologies, such as cell reprogramming and state-of-the-art genome editing, are helping us to address unanswered questions.

TabPath: interactive tables for metabolic pathway analysis.

Motivation: Information about metabolic pathways in a comparative context is one of the most powerful tool to help the understanding of genome-based differences in phenotypes among organisms. Although several platforms exist that provide a wealth of information on metabolic pathways of diverse organisms, the comparison among organisms using metabolic pathways is still a difficult task. Results: We present TabPath (Tables for Metabolic Pathway), a web-based tool to facilitate comparison of metabolic pathways in genomes based on KEGG. From a selection of pathways and genomes of interest on the menu, TabPath generates user-friendly tables that facilitate analysis of variations in metabolism among the selected organisms. Availability and implementation: TabPath is available at http://200.239.132.160:8686. Contact: lmmorei@gmail.com.

XPD/ERCC2 mutations interfere in cellular responses to oxidative stress.

Nucleotide excision repair (NER) is a conserved, flexible mechanism responsible for the removal of bulky, helix-distorting DNA lesions, like ultraviolet damage or cisplatin adducts, but its role in the repair of lesions generated by oxidative stress is still not clear. The helicase XPD/ERCC2, one of the two helicases of the transcription complex IIH, together with XPB, participates both in NER and in RNA pol II-driven transcription. In this work, we investigated the responses of distinct XPD-mutated cell lines to the oxidative stress generated by photoactivated methylene blue (MB) and KBrO3 treatments. The studied cells are derived from patients with XPD mutations but expressing different clinical phenotypes, including xeroderma pigmentosum (XP), XP and Cockayne syndrome (XP-D/CS) and trichothiodystrophy (TTD). We show by different approaches that all XPD-mutated cell lines tested were sensitive to oxidative stress, with those from TTD patients being the most sensitive. Host cell reactivation (HCR) assays showed that XP-D/CS and TTD cells have severely impaired repair capacity of oxidised lesions in plasmid DNA, and alkaline comet assays demonstrated the induction of significantly higher amounts of DNA strand breaks after treatment with photoactivated MB in these cells compared to wild-type cells. All XPD-mutated cells presented strong S/G2 arrest and persistent γ-H2AX staining after photoactivated MB treatment. Taken together, these results indicate that XPD participates in the repair of lesions induced by the redox process, and that XPD mutations lead to differences in the response to oxidatively induced damage.

Congenital cutaneous pyogenic granuloma: Report of two cases and review of the literature.

Congenital cutaneous pyogenic granuloma is a rare benign vascular tumor with clinical and histopathological features similar to infantile hemangioma. It usually presents as a red, pedunculated and highly friable papule. On histopathological analysis, one can see a capillary vessel proliferation with lobular pattern and endothelial proliferation. The differential diagnosis is based on negativity of glucose transporter 1 (GLUT1) immunochemistry studies. We report two infants with congenital pyogenic granuloma, one with a unique cutaneous lesion and the other with multiple lesions affecting both skin and mucosal surfaces. These two cases highlight the importance of the differential diagnosis based on the GLUT1 immunochemistry analysis considering the distinct treatments required to these infant vascular tumors.

The Role of Liver Transplantation in Propionic Acidemia.

Despite optimal medical treatment and strict low-protein diet, the prognosis of propionic acidemia (PA) patients is generally poor. We aim to report our experience with liver transplantation (LT) in the management of PA patients. Six patients with PA received a LT at a mean age of 5.2 years (1.3-7.5 years). The indications for LT were frequent metabolic decompensations in the first 4 patients and preventative in the last 2 patients. Two patients presented hepatic artery thromboses that were solved through an interventional radiologist approach. These patients showed a very high procoagulant state that was observed by thromboelastography. Arterial vasospasm without thrombus was observed in 2 patients during the LT surgery. In order to avoid hepatic artery thrombosis, an arterial conduit from the recipient aorta to the hepatic artery of the donor was used in the fifth patient. After LT, patients presented improvement in propionyl byproducts without complete normalization, but no decompensations have been observed. In conclusion, LT could be a good therapeutic option to improve the metabolic control and the quality of life of PA patients. Improved surgical strategies along with new techniques of interventional radiology allow us to perform the LT minimizing the complications derived from the higher risk of hepatic artery thrombosis.

DNA Adduct Formation in the Lungs and Brain of Rats Exposed to Low Concentrations of [13C2]-Acetaldehyde.

Air pollution is a major environmental risk for human health. Acetaldehyde is present in tobacco smoke and vehicle exhaust. In this study, we show that [13C2]-acetaldehyde induces DNA modification with the formation of isotopically labeled 1, N2-propano-2'-deoxyguanosine adducts in the brain and lungs of rats exposed to concentrations of acetaldehyde found in the atmosphere of megacities. The adduct, with the addition of two molecules of isotopically labeled acetaldehyde [13C4]-1, N2-propano-dGuo, was detected in the lung and brain tissues of exposed rats by micro-HPLC/MS/MS. Structural confirmation of the products was unequivocally performed by nano-LC/ESI+-HRMS3 analyses. DNA modifications induced by acetaldehyde have been regarded as a key factor in the mechanism of mutagenesis and may be involved in the cancer risks associated with air pollution.

Mate tea (Ilex paraguariensis) improves bone formation in the alveolar socket healing after tooth extraction in rats.

OBJECTIVES: The objective of this study was to investigate the effects of mate tea (MT) [Ilex paraguariensis] on alveolar socket healing after tooth extraction. MATERIALS AND METHODS: Sixteen male rats were divided into MT and control groups. MT was administered by intragastric gavage at a dose of 20 mg/kg/day for 28 days before and 28 days after right maxillary incisor extraction. The control group received an equal volume of water. Histopathological and histometric analysis of the neoformed bone area and osteocyte density were performed, as well as immunohistochemical analysis of osteocalcin (OCN), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and manganese superoxide dismutase (MnSOD) in the alveolar socket. Calcium, phosphorus, alkaline phosphatase (ALP) activity, total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in plasma, whereas TRAP activity was determined in serum. RESULTS: Histometry evidenced an increase in bone area (P < 0.0001) and osteocyte density (P < 0.0001). MT increased immunolabeling of MnSOD (P < 0.001), OCN (P < 0.0001), RANKL (P < 0.001), OPG (P < 0.0001), and TRAP (P < 0.001). Calcium and phosphorus concentrations did not differ between the groups. In addition, MT enhanced ALP (P < 0.05) and TRAP (P < 0.0001) activities. MT increased the TAC (P < 0.001), whereas it reduced MDA concentrations (P < 0.0001). CONCLUSIONS: MT increases bone area and osteocyte density in the alveolar socket healing on day 28 after tooth extraction. CLINICAL RELEVANCE: Regular MT ingestion improves the antioxidant defenses and bone formation, which is beneficial for alveolar socket bone healing after tooth extraction.

To warm on the rocks, to cool in the wind: Thermal relations of a small-sized lizard from a mountain environment.

Rising temperatures accompanying global climate change are expected to affect mountain lizards. Therefore, basic information on how these ectotherms deal with their thermal environment is important for further management. We conducted a field study to evaluate how body temperature of the small-sized mountain lizard Eurolophosaurus nanuzae relates to the thermal environment. After capture, the body temperature of the lizards was measured immediately, quickly followed by the substrate and air temperatures, wind intensity, and solar radiation at the capture locations. Linear relationships showed that the body temperature of individuals was positively related to rocky substrate temperatures but negatively related to wind speed. However, air temperature and solar radiation were unrelated to body temperature. Although the substrate is an important heat source for E. nanuzae, in an open environment it can reach temperatures up to 10 °C above the maximum body temperatures of lizards, and can thus be a low-quality thermal substrate. However, individuals seemed to use wind as a cooling source to counterbalance the risks of overheating from high substrate temperatures. As the montane environment that E. nanuzae inhabits seems to have hotter temperatures than those preferred by the species, lizards should benefit from the cooling winds to keep their body temperature at appropriate levels. Different to previous studies that evaluated wind effects on body temperatures of lizards, our results showed that winds seemed to promote thermoregulation for E. nanuzae.

Biotechnological potential of plant growth-promoting bacteria from the roots and rhizospheres of endemic plants in ironstone vegetation in southeastern Brazil.

Microorganisms associated with plants have a great biotechnological potential, but investigations of these microorganisms associated with native plants in peculiar environments has been incipient. The objective of this study was to analyze the plant growth-promoting bacteria potential of cultivable bacteria associated with rare plants from the ferruginous rocky fields of the Brazilian Iron Quadrangle. The roots and rhizospheres of nine endemic plants species and samples of a root found in a lateritiric duricrust (canga) cave were collected, the culturable bacteria isolated and prospected for distinct biotechnological and ecological potentials. Out of the 148 isolates obtained, 8 (5.4%) showed potential to promote plant growth, whereas 4 (2.7%) isolates acted as biocontrol agents against Xanthomonas citri pathotype A (Xac306), reducing the cancrotic lesions by more than 60% when co-inoculated with this phytopathogen in Citrus sinensis plants. Moreover, other 4 (2.7%) isolates were classified as potential bioremediation agents, being able to withstand high concentrations of arsenite (5 mM As3+) and arsenate (800 mM As5+), by removing up to 35% and 15% of this metalloid in solution, respectively. These same four isolates had a positive influence on the growth of both the roots and the aerial parts when inoculated with tomato seeds in the soil contaminated with arsenic. This is the first time that an investigation highlights the potentialities of bacteria associated with rare plants of ferruginous rocky fields as a reservoir of microbiota of biotechnological and ecological interest, highlighting the importance of conservation of this area that is undergoing intense anthropic activity.

Proteomics-based identification of differentially abundant proteins reveals adaptation mechanisms of Xanthomonas citri subsp. citri during Citrus sinensis infection.

BACKGROUND: Xanthomonas citri subsp. citri (Xac) is the causal agent of citrus canker. A proteomic analysis under in planta infectious and non-infectious conditions was conducted in order to increase our knowledge about the adaptive process of Xac during infection. RESULTS: For that, a 2D-based proteomic analysis of Xac at 1, 3 and 5 days after inoculation, in comparison to Xac growth in NB media was carried out and followed by MALDI-TOF-TOF identification of 124 unique differentially abundant proteins. Among them, 79 correspond to up-regulated proteins in at least one of the three stages of infection. Our results indicate an important role of proteins related to biofilm synthesis, lipopolysaccharides biosynthesis, and iron uptake and metabolism as possible modulators of plant innate immunity, and revealed an intricate network of proteins involved in reactive oxygen species adaptation during Plants` Oxidative Burst response. We also identified proteins previously unknown to be involved in Xac-Citrus interaction, including the hypothetical protein XAC3981. A mutant strain for this gene has proved to be non-pathogenic in respect to classical symptoms of citrus canker induced in compatible plants. CONCLUSIONS: This is the first time that a protein repertoire is shown to be active and working in an integrated manner during the infection process in a compatible host, pointing to an elaborate mechanism for adaptation of Xac once inside the plant.

Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus.

PURPOSE: We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus. METHODS: Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies. RESULTS: The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group. CONCLUSIONS: We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

Environmental enrichment reduces brain damage in hydrocephalic immature rats.

PURPOSE: We investigate the effects of environmental enrichment (EE) on morphological alterations in different brain structures of pup rats submitted to hydrocephalus condition. METHODS: Hydrocephalus was induced in 7-day-old pup rats by injection of 20% kaolin into the cisterna magna. Ventricular dilatation and magnetization transfer to analyze myelin were assessed by magnetic resonance. Hydrocephalic and control rats exposed to EE (n = 10 per group) were housed in cages with a tunnel, ramp, and colored plastic balls that would emit sound when touched. The walls of the housing were decorated with colored adhesive tape. Moreover, tactile and auditory stimulation was performed daily throughout the experiment. Hydrocephalic and control rats not exposed to EE (n = 10 per group) were allocated singly in standard cages. All animals were weighed daily and exposed to open-field conditions every 2 days until the end of the experiment when they were sacrificed and the brains removed for histology and immunohistochemistry. Solochrome cyanine staining was performed to assess the thickness of the corpus callosum. The glial fibrillary acidic protein method was used to evaluate reactive astrocytes, and the Ki67 method to assess cellular proliferation in the subventricular zone. RESULTS: The hydrocephalic animals exposed to EE showed better performance in Open Field tests (p < 0.05), while presenting lower weight gain. In addition, these animals showed better myelination as revealed by magnetization transfer (p < 0.05). Finally, the EE group showed a reduction in reactive astrocytes by means of glial fibrillary acidic protein immunostaining and preservation of the proliferation potential of progenitor cells. CONCLUSION: The results suggest that EE can protect the developing brain against damaging effects caused by hydrocephalus.

Toxicity of two effluents from agricultural activity: Comparing the genotoxicity of sugar cane and orange vinasse.

Vinasse, produced by several countries as a by-product of agricultural activity, has different alternatives for its reuse, mainly fertirrigation. Several monocultures, such as sugar cane and orange crops, produce this effluent. Sugar cane vinasse is already widely used in fertirrigation and orange vinasse has potential for this intention. However, its use as a fertilizer has caused great concern. Thus, ecotoxicological evaluation is extremely important in order to assess the possible effects on the environment. Therefore, the aim of this study was to evaluate the potential toxicity of vinasse of two different crops: sugar cane and orange. For this purpose, bioassays with Allium cepa as a test organism were performed with two vinasse dilutions (2.5% and 5%) to detect chromosomal aberrations and micronucleus induction. The results showed that both types of vinasse are able to induce chromosomal aberrations in meristematic cells, mainly nuclear and anaphasic bridges, suggesting genotoxic potential. The induction of micronuclei in cells of the F1 region suggests that the two residues have mutagenic potential. Thus, caution is advised when applying these effluents in the environment.

Ventricular-subcutaneous shunt for the treatment of experimental hydrocephalus in young rats: technical note.

BACKGROUND: Hydrocephalus is a complex disease that affects cerebrospinal fluid (CSF) dynamics and is very common in children. To this date, CSF shunting is still the standard treatment for childhood hydrocephalus, but, nevertheless, the effects of such an operation on the developing brain are widely unknown. To help overcome this, experimental models of CSF shunts are surely very useful tools. OBJECTIVE: The objective of this study was to describe a feasible and reliable technique of an adapted ventricular-subcutaneous shunt for the treatment of kaolin-induced hydrocephalus in young rats. METHODS: We developed a ventricular-subcutaneous shunt (VSCS) technique which was used in 31 Wistar young rats with kaolin-induced hydrocephalus. Hydrocephalus was induced at 7 days of age, and shunt implantation was performed 7 days later. Our technique used a 0.7-mm gauge polypropylene catheter tunneled to a subcutaneous pocket created over the animal's back and inserted into the right lateral ventricle. All animals were sacrificed 14 days after shunt insertion. RESULTS: Twenty-four rats survived and remained well until the study was ended. No major complications were seen. Their weight gain went back to normal. They all underwent ambulatory behavioral testing prior and after VSCS, which showed improvement in their motor skills. We have also obtained magnetic resonance (MR) scans of 16 pups confirming reduction of ventricular size after shunting and indicating effective treatment. Histopathological analysis of brain samples before and after shunting showed reversion of ependymal and corpus callosum disruption, as well as fewer reactive astrocytes in shunted animals. CONCLUSIONS: An experimental CSF shunt technique was devised. Excessive CSF of hydrocephalic rats is diverted into the subcutaneous space where it can be resorbed. This technique has a low complication rate and is effective. It might be applied to various types of experimental studies involving induction and treatment of hydrocephalus.