The recent tissue-engineering approaches related to acute neural injuries, especially traumatic spinal cord injuries, involve an amalgamation of several complex interventional strategies including polymeric scaffolds, micro- and nanoparticulate systems, and stem cell grafts which can be combinatorially termed as "bioactive polymer nanocomposites". The chapter highlights important developments in various polymeric or biomaterial archetypes in combination with nanomediated bioactive delivery and structural support systems. These versatile and advanced polymeric nanocomposites are capable of carrying and delivering a range of biological and bioactive cargo ranging from, but not limited to, stem cells through biofactors to glucocorticoids. In addition to the bioactive reservoir function, the nanostructures when added to polymeric scaffolds augment their neurosupport function by providing nanotopograhical surfaces, neurophysicochemical cues, mechanical strength, and directional neuronal growth opportunities to allow axonal growth and conformal repair. The chapter further explores the future of polymeric nanocomposites in terms of designing neuroactive nanoparticles as well as nanostructured scaffolds with inherent 3D nanoassembling characteristics which can provide the much needed standalone "multi-functional combinatorial device" for effective neuroregeneration and neural repair.

All book chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. However, users who aim to disseminate and distribute copies of this book as a whole must not seek monetary compensation for such service (excluded OMICS Group representatives and agreed collaborations). After this work has been published by OMICS Group, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Statements and opinions expressed in the book are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book.

Among Spinal Cord Injury (SCI) intervention the administration of high-dose high-potency steroidal drugs such as methylprednisolone or dexamethasone is used to reduce the inflammation associated with primary injury and prevention of the subsequent secondary injury. The administration of steroids has several side-effects that jeopardize their use and therefore safer chemical neuro-entities are required. Natural compounds such as curcumin (anti-oxidant) and quercetin (anti-inflammatory) have been investigated as alternative neuroactive, but are not as potent as the steroids. Hence, they are required in very high doses which may lead to significant toxicity causing an increase in cellular levels of reactive oxygen species, active iron chelation, inhibiting the activity of the cytochrome P450 enzymes such as glutathione-S-transferase and UDP-glucuronosyltransferase. A reduction in the dose of these neuroactives is possible with the administration of a 'chemically-variant' permutation with additive or synergistic therapeutic benefits. Therefore, we hypothesize that curcumin and quercetin, both natural polyphenolic flavonoids, can "additively and synergistically" improve the physiological outcome after traumatic SCI when used in combination and termed 'Cur(Que)min' - thereby decreasing the dose levels and hence reducing the inherent high dose-cytotoxicity of the individual neuroactives. This hypothesis provides the first-account of a curcumin-quercetin combination for SCI intervention theorizing the possible biomolecular-mechanism that may provide the scientific community with a novel neuroprotective and neurotherapeutic treatment option for SCI.

International Journal of Developmental NeuroscienceVolume 30, Issue 8 p. 674-675 Abstract ISDN2012_0186: A combinatorial in silico approach to model the glycosylated nornicotine-curcumin paradigm in neuroprotection and neurotherapy for Alzheimer's disease P. Kumar, Corresponding Author P. Kumar pradeep.kumar@students.wits.ac.za Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown, Johannesburg, South Africa ⁎Corresponding author. E-mail address:pradeep.kumar@students.wits.ac.za (P. Kumar)Search for more papers by this authorV. Pillay, V. Pillay Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown, Johannesburg, South AfricaSearch for more papers by this authorY.E. Choonara, Y.E. Choonara Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown, Johannesburg, South AfricaSearch for more papers by this authorL.C. du Toit, L.C. du Toit Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown, Johannesburg, South AfricaSearch for more papers by this authorG. Modi, G. Modi Department of Neurology, University of the Witwatersrand, Parktown, Johannesburg, South AfricaSearch for more papers by this authorD. Naidoo, D. Naidoo Department of Neurosurgery, University of the Witwatersrand, Parktown, Johannesburg, South AfricaSearch for more papers by this author P. Kumar, Corresponding Author P. Kumar pradeep.kumar@students.wits.ac.za Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown, Johannesburg, South Africa ⁎Corresponding author. E-mail address:pradeep.kumar@students.wits.ac.za (P. Kumar)Search for more papers by this authorV. Pillay, V. Pillay Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown, Johannesburg, South AfricaSearch for more papers by this authorY.E. Choonara, Y.E. Choonara Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown, Johannesburg, South AfricaSearch for more papers by this authorL.C. du Toit, L.C. du Toit Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown, Johannesburg, South AfricaSearch for more papers by this authorG. Modi, G. Modi Department of Neurology, University of the Witwatersrand, Parktown, Johannesburg, South AfricaSearch for more papers by this authorD. Naidoo, D. Naidoo Department of Neurosurgery, University of the Witwatersrand, Parktown, Johannesburg, South AfricaSearch for more papers by this author First published: 17 January 2013 https://doi.org/10.1016/j.ijdevneu.2012.10.014Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume30, Issue8Abstracts to the 19th Biennial Meeting of the International Society for Developmental Neuroscience, 11-14 January 2012, Mumbai, IndiaDecember 2012Pages 674-675 RelatedInformation

BACKGROUNDNon-traumatic myelopathy from developing regions has been described widely. In these regions infections, mainly tuberculosis, followed by acute transverse myelitis and neoplasms, dominate. These are also regions of high HIV prevalence. In developed regions, the most prominent reported spinal cord disease in HIV/AIDS is vacuolar myelopathy (VM). Other myelopathy causes in HIV/AIDS include opportunistic infections, neoplasms, vascular lesions and metabolic disease. In developing regions, opportunistic infections are more commonly encountered with VM occurring less frequently.AIMTo determine the influence of HIV on the myelopathy spectrum in an HIV endemic region.DESIGNProspective case series.METHODSHundred unselected consecutive in-patients admitted with myelopathy were studied. Myelopathy aetiologies were established by collating information obtained from magnetic resonance imaging (MRI) scans, CSF and blood studies, CXR findings, non-neurological illness and response to treatment. Data were analysed in terms of two cohorts, HIV positive and HIV negative.RESULTSApproximately 50% of the patients presenting and admitted to our hospital with non-traumatic myelopathy are HIV positive. The HIV positive myelopathy patients were younger (20-40 years) and had infectious aetiologies. Tuberculosis was the most frequently identified cause of myelopathy. The majority of HIV-positive patients had advanced HIV infection. Anti-retroviral treatment did not influence myelopathy aetiologies. The HIV-negative patients were older and had neoplasms, followed by degenerative spondylosis as the main myelopathy causes.CONCLUSIONHIV influences the non-traumatic myelopathy spectrum in regions with high HIV prevalence. Empiric treatment of HIV-myelopathy patients with anti-tuberculous medications where resources are severely limited has merit.

Neurocysticercosis commonly presents with seizures resulting from cystic or calcified parenchymal brain lesions. Here we describe a patient with intraventricular neurocysticercosis causing acute unilateral hydrocephalus and discuss diagnosis, imaging and management.

The purpose of this study was to design, characterize and assess the influence of triethanolamine (TEA) on the physicomechanical properties and release of methotrexate (MTX) from a composite biopolymeric membrane. Conjugated poly(L-lactic acid) (PLLA) and poly(vinyl alcohol) (PVA) membranes were prepared by immersion precipitation with and without the addition of TEA. Drug entrapment efficiency (DEE) and release studies were performed in phosphate buffered saline (pH 7.4, 37 degrees C). Scanning electron microscopy elucidated the membrane surface morphology. Computational and structural molecular modeling rationalized the potential mechanisms of membrane formation and MTX release. Bi-axial force-distance (F-D) extensibility profiles were generated to determine the membrane toughness, elasticity and fracturability. Membranes were significantly toughened by the addition of TEA as a discrete rubbery phase within the co-polymer matrix. MTX-TEA-PLLA-PVA membranes were tougher (F = 89 N) and more extensible (D = 8.79 mm) compared to MTX-PLLA-PVA (F = 35 N, D = 3.7 mm) membranes as a greater force of extension and fracture distance were required (N = 10). DEE values were relatively high (>80%, N = 5) for both formulations. Photomicrographs revealed distinct crystalline layered morphologies with macro-pores. MTX was released by tri-phasic kinetics with a lower fractional release of MTX from MTX-TEA-PLLA-PVA membranes compared to MTX-PLLA-PVA. TEA provided a synergistic approach to improving the membrane physicomechanical properties and modulation of MTX release. The composite biopolymeric membrane may therefore be suitable for the novel delivery of MTX in the treatment of chronic primary central nervous system lymphoma.

Background and purpose: Aneurysms have been described in HIV infected patients. These involve predominantly extracranial blood vessels with specific histological and clinical features. Intracranial aneurysms are rare and have been identified mainly in children. Methods: Case reports and literature review. Results: Three black South African HIV positive adult patients with intracranial aneurysms were identified. The clinical, laboratory and radiological features are described. Conclusions: Intracranial aneurysms occur in both adults and children infected with HIV. More information is required on this association. The frequency in terms of numbers of cases indicates that it is an uncommon association or manifestation of HIV. The characteristics of the aneurysms suggest that they are distinctive and not a chance or coincidental co-occurrence of congenital or arteriosclerotic aneurysms.

Toxoplasma seroprevalence was determined in 307 consecutive HIV-infected medical inpatients at the Helen Joseph Hospital, Johannesburg, South Africa, using an enzyme linked immunosorbent assay to detect immunoglobulin G (IgG) and IgM antibodies. The mean age of patients was 36 years, with a female to male ratio of 1.3 to 1. The mean CD4 count was 109 cells/mL. Toxoplasma antibodies were detected in 25 patients (8%). Twenty-two of these patients were IgG positive and IgM negative, i.e. reactivation toxoplasmosis. Only two patients (0.65%) had clinical manifestations of toxoplasmosis (one toxoplasma encephalitis and one retinitis). The risk for toxoplasma encephalitis (TE) was 0.33%. These results indicate that the toxoplasma seroprevalence and the TE risk in this population is low. The implication from this study is that in HIV-infected populations where the toxoplasma seroprevalence is low, the TE risk will be low and empiric treatment of focal brain lesions with anti-toxoplasma therapy may be inappropriate.

Intracranial tuberculosis is an important cause of morbidity and mortality in developing countries where tuberculosis is endemic. In the central nervous system tuberculosis manifests as cerebritis, cerebral abscess, tuberculoma, and tuberculous meningitis (TBM). TBM is thought to arise from cerebrospinal fluid (CSF) seeding of a ruptured pial or subependymal granuloma. Tuberculomata result from haematogenous dissemination and histologically are granulomas with central areas of caseous necrosis. Tuberculomata may develop whilst patients are on treatment for TB. The co-occurrence of intracranial tuberculoma and TBM is well recognized. Medical therapy is effective for both forms, with a high cure rate in TBM, and a regression in size of the lesion with improvement of neurological deficit in tuberculoma. Deterioration in patients with TBM is caused by the development of obstructive hydrocephalus or cerebral infarction on the basis of endarteritis. Deterioration in patients with tuberculoma may result from paradoxical expansion of the lesion, poor treatment compliance, and postulated haemorrhage into the tuberculoma. Intracranial haemorrhage as a complication of TBM has been described, albeit rarely. There are a few case reports of patients with TBM complicated by intraventricular, intracerebral and subarachnoid haemorrhage on an aneurysmal or non-aneurysmal basis. We describe here a patient with TBM and an associated left cerebellar tuberculoma who suddenly deteriorated and died on treatment. A large haemorrhage involving the right cerebellum, with subarachnoid extension was demonstrated on computed tomography (CT) scan of the brain and at postmortem. These findings are discussed with respect to the possible mechanism/s of haemorrhage in intracranial tuberculosis. Case report

The purpose of the study was to determine the relevance of protein S deficiency in HIV infected patients with ischaemic stroke. In total, 33 HIV positive patients with ischaemic stroke, previously described by us, were prospectively compared with control groups for occurrence of protein S deficiency. The control groups comprised an equal number of consecutive matched HIV positive and negative patients without and with stroke respectively. Data were analysed in contingency tables using Fisher’s exact test. Protein S deficiency occurred significantly more frequently in HIV positive compared with HIV negative stroke patients (p<0.001). However, by including HIV positive patients without stroke as a control group and comparing this group with the HIV positive stroke group we found that protein S deficiency is statistically related to HIV infection and not stroke occurrence. Our data indicate that the presence of protein S deficiency in HIV positive patients with stroke is an epiphenomenon of HIV infection.

Background. HIV-associated focal brain lesions (FBLs) are caused by opportunistic infections, neoplasms, or cerebrovascular diseases. In developed countries toxoplasma encephalitis (TE) is the most frequent cause followed by primary CNS lymphoma (PCNSL). Guidelines based on these causes have been proposed and successfully implemented. These guide-lines do not consider the causes of HIV-associated FBL in developing countries where treatable infections predominate. The guidelines as proposed would adversely influence outcome if applied to patients in developing countries.Objective. To determine a practical approach to the management of HIV-associated FBLs in developing countries.Design. Prospective case series.Methods. Management based on presumed aetiologies of the FBLs determined by collating information obtained from computed tomography (CT) scans, cerebrospinal fluid and blood studies, concurrent non-neurological illness and response to treatment.Results. The principal presumed cause of FBL was tuberculosis (TB) (69%), and the therapeutic response was good in 69% of patients.Conclusions. In developing countries infections are the predominant cause of HIV-associated FBL. The principal cause is determined by the infection that is endemic to the population being studied. Empiric treatment based on limited investigations should be directed according to the nature of this infection. A modified algorithm is proposed.

Background: HIV-associated focal brain lesions (HFBL) are caused by opportunistic infections, neoplasms, or cerebrovascular diseases. In developed countries, toxoplasma encephalitis (TE) is the most frequent cause, followed by primary CNS lymphoma (PCNSL). Guidelines based on these causes however are poorly suited to developing countries, where treatable infections predominate as causes of HFBL.Aim: To determine a practical approach to the management of HFBL in developing countries.Design: Case series.Methods: Patients (n = 32) were managed based on presumed aetiologies of the focal brain lesions, determined by collating information from CT scans, CSF and blood studies, concurrent non-neurological illness and response to treatment.Results: The principal presumed cause of HFBL was tuberculosis (69%). The therapeutic response was good in 69% of patients.Discussion: In developing countries, infections are the predominant cause of HFBL, the principal causes being infections that are endemic to the populations being studied. Empiric treatment based on limited investigations should be directed according to the nature of such infections. A modified algorithm is proposed.