Dr Marissa  Balmith 

https://orcid.org/0000-0002-9209-7318

Dr Brian Flepisi

https://orcid.org/0000-0002-0628-4636

The blood-brain barrier (BBB) is a collection of anatomical barriers and transport systems within the endothelium of cerebral vasculature. It is the tightest endothelial barrier in the human body, with high transendothelial electrical resistance and low permeability, owing to the properties of the endothelial cells lining the cerebral vasculature. It confers strict, selective control over the transport of substances into and out of the brain parenchyma. The BBB is responsible for preventing the entry of neurotoxins, metabolic waste, cells and pathogens present in the peripheral circulation into the central nervous system (CNS). Our research focuses on the development and validation of an in vitro model of the BBB. The aim is to develop a BBB co-culture model that accurately replicates the properties of the BBB in vivo. This model may be useful in improving the understanding of the BBB, as well as understanding the role it plays in the pathogenesis of neurological diseases, and furthering knowledge of interactions between components of the neurovascular unit. In addition, this model will be used in determining the effects of cancer and neurological conditions on the BBB, as well as the effects of various drugs including CNS drugs and phytomedicine.

THE EFFECT OF CANCER ON THE BLOOD-BRAIN BARRIER

It is well established that cancer is the leading cause of death worldwide, accounting for more than 8 million deaths. Amid the most common cancers are the central nervous system (CNS) cancers with increasing incidence in both children and young adults. Approximately one-third of CNS cancers are malignant, and the remainder are either benign or borderline malignant. Our research focuses mainly on CNS cancers such as glioblastoma and neuroblastoma, as well as cancers that originate from distant sites and more likely to metastasise to the brain such as breast and lung cancers. Primary CNS cancerous cells are known to penetrate the BBB and metastasise to distant part of the body, while the secondary brain cancer cells penetrate the BBB to gain entry into the brain. The mechanisms by which these cancerous cells disrupt and cross the BBB are not well understood. It has been suggested that cancers regardless of their origin may affect the integrity of the BBB. With its integrity disturbed, the BBB may allow toxic molecules and substances to enter the brain. Thus, we aim to investigate the effects of cancerous cells on the integrity of the BBB and the mechanisms by which cancerous cells disrupt it.

Collaborators: Prof David Fischer (Medical Biosciences, UWC), Prof Peace Mabeta (Physiology, UP), Dr Iman van den Bout (Physiology, UP)

Applicable research levels: Basic sciences research at Hons, MSc or PhD level

Minimum skillsets at MSc and PhD levels: Cell culture (most preferred), spectrometric methods, microscopy (light and fluorescence), and/or Western blotting, and/or permeability assays (trans-endothelial electrical resistance, and sodium fluorescein) (advantageous)

Students: Ms Jaime de Carvalho (MSc candidate); Vacancy available

Resources: https://scimedjournal.org/index.php/SMJ/article/view/337

https://ouci.dntb.gov.ua/en/works/7Wk6KAZ7/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698446/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773645/

https://journals.co.za/doi/epdf/10.36303/SAGP.2021.2.6.0095

THE EFFECT OF CNS DISEASE DRUGS ON THE BLOOD-BRAIN BARRIER

Drug delivery to the CNS remains a challenge in the treatment of neurological diseases such as Alzheimer’s diseases, Parkinson’s disease, epilepsy, depression, cancer, and stroke due to the presence of BBB. Thus, it may hinder the progress in the development of new therapeutics for CNS disorders. In contrary, drugs of abuse have been shown to increase the permeability of BBB resulting in the susceptibility of CNS to foreign molecules and increasing the influx of systemic toxins into the brain. The mechanisms by which the drugs of abuse disrupt the BBB are not well elucidated. This study aims to determine the effects of CNS disease drugs on the BBB, drug delivery strategies through the BBB, and the mechanisms by which the drugs of abuse affect the integrity of the BBB in vitro.

Collaborators: Prof David Fischer (Medical Biosciences, UWC)

Applicable research levels: Basic sciences research at Hons, MSc or PhD level

Minimum skillsets at MSc and PhD levels: Cell culture (most preferred); spectrometric methods, microscopy (light and fluorescence), and/or Western blotting, and/or permeability assays (trans-endothelial electrical resistance, and sodium fluorescein) (advantageous), LC/MS-MS

Students: Vacancy available

THE EFFECT OF PHYTOMEDICINE ON THE BLOOD-BRAIN BARRIER

Research has unveiled the capacity of certain plant-derived phytochemicals to interact with the BBB, either by modulating its permeability or by influencing transporters that govern the entry of molecules into the brain. Understanding the interplay between phytochemicals and the BBB holds significant promise, not only for elucidating the neuroprotective properties of specific plant compounds but also for potentially advancing drug delivery strategies for neurological disorders and conditions that require precise targeting within the brain. Our research aims to determine the effects of selected plant extracts on brain endothelial cells in vitro.

Collaborators:  Dr Sylvester Ifeanyi Omoruyi (Anatomy, Wits University)

Applicable research levels:  Basic sciences research at Hons, MSc, and PhD levels

Minimum skillsets at MSc level:  Basic sciences research (plant extraction, fractionation, cell culture, cytotoxicity testing, microscopy, Western blotting, flow cytometry, LC/MS-MS, permeability assays (trans-endothelial electrical resistance, and sodium fluorescein)

Students: Vacancy available