Neuroscience and neurological disorders – Academia Plus Educational Services

Neurological disease is the second leading cause of death and disability worldwide. The increasing global burden of brain diseases such as stroke, Alzheimer’s and multiple sclerosis, implies the need for better therapeutic strategies in the management of the disease pathology. To date, delivery of therapeutic molecules and drugs across the blood-brain barrier (BBB) – the barrier that separates the brain from the rest of the body- remains a challenge. In this article, we will understand the different ways in which this barrier can be crossed if a substance has to enter the cerebral world, especially for therapeutic purposes.

Though the concept of BBB was discovered back in the 19th century by Paul Ehrlich, the understanding of it is still evolving. Initially, the blood-brain barrier was simply considered to be comprised of tight junctions of cells which could not be penetrated. Later studies revealed that there may actually be transporters or gatekeepers, that decide the entry and exit of substances into the brain.

However, we also know that despite the tight regulation of transport into the cerebral world, certain bacteria, viruses and fungi can pass through and cause infection. Some examples include- Meningitis, encephalitis and viral-induced glioblastoma.

A common mode of entry for the microbes is mediated by specialized gatekeepers of the BBB known as receptors. Mimicking these interactions, researchers have tried to develop nano-carriers coated with microbes to send therapeutic molecules across the BBB in order to help in their targeted slow release in different regions of the brain. This approach has been successful and efficient to some extent, however, the approach fails especially in case of Alzheimer’s or stroke, where the integrity of BBB itself is affected and therefore the release of therapeutic molecules can become unspecific.

Nevertheless, leaving the microbes aside for a while, have you ever wondered how our inherent blood cells themselves cross the blood-brain barrier? Could it be possible to mimic their process for drug delivery?

The answer is yes!

Several drug delivery studies have focused on mimicking the entry of blood cells into the brain. In the case of the treatment of brain tumours, for example, the nano-carriers use receptors that are inherently used by the blood cells to deliver therapeutic molecules such as neurotoxins. Such a targeted delivery to the tumor regions reduces the off-target effects of the neurotoxin, killing only the tumor cells.

Now, one may also ask whether the Blood-brain barrier only plays the role of a gatekeeper, or does it have other roles as well?

Further studies on BBB unravel that there is a tight interaction between the different cells of the brain, called neovascular units. pericytes, astrocytes, glial and endothelial cells making a neovascular unit. These neo-vascular units of BBB serve as a junction to relay and transmit important signals to the brain. Thus, the dynamic nature of these barriers opens up new avenues for therapeutic intervention in neurological disorders. Several neurological disorders occur due to the dysfunction of BBB, hence repair and the delivery of therapeutics to the BBB itself could become a therapeutic solution. For example, in diseases like multiple sclerosis, the integrity of the BBB needs to decrease in order to prevent inflammation and curb the disease. Thus, BBB holds a vital role in maintaining the physiology of the brain, beyond being just a ‘barrier’ or a ‘gatekeeper’.

Despite the numerous advancements in the understanding of BBB, the efficiency of drug delivery remains undermined due to the difficulty in modelling the multidimensional structures of BBB. Hence further development of efficient models with recent understandings of BBB structure is required to improve targeted drug treatments for neurological disorders.

Keerthana B Writer

Disclaimer: The content of this article is meant for educational and creative purposes only, and will not be directly used for generation of profits. All rights and responsibilities, including the authenticity of the information presented in this article belong to the original authors and their publications (listed below in the Bibliography section), and there is no copyright infringement intended.

Bibliography

Don’t we all recognize people by their faces almost effortlessly? Don’t we search for familiar faces in a party to help blend into the crowd and socialise further? Well rest assured, you are not alone!

But, what if I told you that it is impossible for few people to do what we often take for granted as a simple task. Scary isn’t it? A neurological disorder called prosopagnosia robs people of this ability. Simply put- prosopagnosia stands for face blindness. The mind of a prosopagnosic person denies having seen a face before, even if it belongs to someone known and this has nothing to do with memory loss. When visualizing a conversation that they had with someone, they are able to recall everything about that instance but their face!

There are two major types of this disorder- acquired and developmental.

Acquired prosopagnosia could be because of a brain injury or any other neurological disorder such as trauma, stroke, tumors etc.

Developmental prosopagnosia, on the other hand might occur during the developmental stages of life and in some cases, could also have genetic origins.

Now, let us dive a little deeper into what this condition is all about. In order to do that, we need to get an insight on how our brain is able to recognise faces in the first place.

Bruce and Young, two scientists, came up with a cognitive model in order to understand the steps involved in face recognition:

Face encoding: In the first step, the structural information about the face is encoded.
Face recognition: In the second step, the structural information is matched to “face recognition units”, which are the stores of face memories in the brain, that determine whether a face has been seen before.
Person identification: In the third step, any familiarity that is recognized in ‘Face recognition’ step, activates a ‘person identity node’, ie. an area of the brain that gives access to the biographical information of the person to whom the face belongs.
Name generation: In the last step, the brain processes or attaches a name to the face, depending upon the first three steps.

The entire process involves a core network and an extended network- broadly speaking, steps 1 and 2 belong to the core network, while the steps 3 and 4 belong to the extended network. Lesions/injuries in certain parts of any one of these networks can lead to different variants of prosopagnosia. Owing to this, there are two variants of prosopagnosia, especially in acquired prosopagnosia:

Apperceptive: a person is unable to recognize/encode the structural information of the face at all, due to an injury in the core network

Associative: a person can encode the face but is unable to associate it with any previous familiarity, due to an injury in the extended network.

In the case of developmental prosopagnosia, no obvious structural lesions are found in either of the networks, however certain abnormalities may be seen in the cortex of the brain itself.

One question in the field of prosopagnosia is whether the patients fail in the recognition of faces only or does this inability extend to other areas as well- which in turn leads us to speculate whether the mechanism to recognize faces is involved in the recognition of objects or is it just “face specific”. As per neuroimaging studies, it has been shown that the cortical network of regions involved in face recognition does partially overlap with those of object recognition but it is still distinct. With that being said, some prosopagnosic patients may or may not have difficulty recognizing objects. Even though words are processed on the left and faces are processed on the right, it has been shown that a bilateral network in both cases does overlap. Again, most patients with acquired prosopagnosia have no problem with word processing while some do. However, people with prosopagnosia are thought to have superior voice recognition due to years of relying on voice cues to recognize others.

Adults and children with this disorder can have other significant implications like traumatic social experiences, chronic anxiety, embarrassment and guilt and usually have a limited social circle because of this inability. Imagine never feeling comfortable around anyone and always having to do ‘small talk’, even with your best friend, because you don’t remember them!

The treatments for improving prosopagnosia differ, depending on the type of prosopagnosia, the variant and intensity of injury at the affected parts. For the acquired variant, most of the training programs usually focus on enhancing coping strategies to deal with poor face recognition. In the case of developmental prosopagnosia, another approach needs to be implemented depending upon the severity.

Nonetheless, counselling sessions for someone who is prosopagnosic or who may have prosopagnosia should be a must as the mental stress associated with this condition can be both overwhelming and confusing. Furthermore, awareness regarding prosopagnosia needs to be increased in order to separate this condition from a simple memory loss. Diagnosis is needed to first rule out the other defects.

When I personally try to view the world through the eyes of someone with prosopagnosia, I imagine walking down a busy street among a thousand faceless people who either remove their hats to greet me or are gesturing to hit me with it, I have no clue since I can’t understand their facial expressions. This seems extremely scary, confusing and moreover, lonely. I sincerely hope this condition is brought to the notice of more and more people and its treatment can be a bit more definite.

Sanjhi Sardana Writer

Bibliography

Tag: Neuroscience and neurological disorders

Entering the cerebral world – learnings from inherent human cells and microbes!

Know all about Prosopagnosia: an inability to recognize faces