Neurological Conditions, Disorders, and Diseases

Neurological conditions are a major global health burden that affects millions worldwide, often leading to disability or death. There are many diseases and disorders that can affect the brain and nervous system, which can be subcategorized into different fields such as neuroimmunology, neuro-oncology, neurovascular, and neurodegenerative research.

Neuroimmunological Disorders

Neuroimmunology focuses on interactions between the nervous and immune systems and includes neurological diseases that involve immune-mediated damage.
These conditions can be caused by an overactive immune system attacking the nervous system (NS) (e.g., multiple sclerosis, MS; Guillain-Barre syndrome), by the NS triggering an immune response (e.g., autoimmune encephalitis), or by suppression of an immune response (e.g., HIV).

The relationship between immune and nervous cells and how they affect and regulate each other plays an important role in the development and manifestation of neuroimmunological diseases. For example, during the development of MS, T-cells attack myelin, the insulation shell of nerve fibers in the central nervous system (CNS). In this process, chemokines produced by activated glial cells and infiltrating immune cells attract T-cells to the CNS. Once they reach the CNS, these immune cells initiate and perpetuate an inflammatory response that leads to demyelination and axonal damage.

Understanding the crosstalk between the nervous and the immune system on a cellular and molecular level is fundamental to developing new therapies and medications.

Neural Injuries

Neural injuries include damage and impairment of the brain, spinal cord, and peripheral nerves. They can be inflicted by trauma (e.g., head injury, spinal cord injury), infections (e.g., meningitis, syphilis), autoimmune disorders (e.g., MS), and tumors (e.g., glioblastoma). The symptoms of neural injuries can vary widely depending on the location and extent of the damage; but may include loss of sensation, muscle weakness or paralysis, cognitive impairment, memory problems, difficulty speaking, and chronic pain.

Treatment options focus on inhibiting the neurodegenerative processes that follow the acute injury. These processes include migration and chemotaxis events that trigger wound healing and axon regrowth. 

Rat fibroblast, surrounded by parallel-aligned rat Schwann cells (SCs), cultured in an ibidi µ-Slide 8 Well and stained for the SC-marker S100 (green), Vimentin (grey), and DAPI (blue). The image was obtained with a laser-scanning microscope.
Courtesy: Flavia Millesi, Medical University Vienna, Austria

Neuro-Oncology

The field of neuro-oncology focuses on understanding the mechanisms of cancerous brain tumor development, growth, and progression, as well as finding new treatments. The complex microenvironment of the brain and the selective permeability of the blood-brain barrier (BBB), which prevents many substances from crossing into the brain, pose a special challenge to developing effective treatments for this disease type.

Glioblastoma is the most common malignant brain cancer in adults. The lack of effective treatments, together with its highly invasive growth in surrounding tissues, results in a low life expectancy after diagnosis. Among other factors, its aggressiveness has been associated with its high motility. Therefore, understanding the underlying mechanisms that lead to this increased motility is crucial for developing effective treatments to target glioblastoma cells’ invasiveness. This includes targeting pathways and molecules involved in, for example, cytoskeletal dynamics and cell adhesion.

An additional approach in glioblastoma treatment focuses on successfully developing methods to deliver drugs across the BBB. Therefore, a deeper understanding of its function and interaction with adjacent tissues is key.

Neurovascular Disorders

Neurovascular conditions, for example, aneurysms or ischemic and hemorrhagic strokes, result from disruptions in the blood vessels and the blood supply to the brain and spinal cord.

The neurovascular unit (NVU) is a functional organization that describes the complex network of neurons, glial cells, vascular endothelial cells, and the extracellular matrix in the brain. It plays a major role in regulating cerebral blood flow, maintaining the integrity of the BBB, and supporting proper neuronal function. Disruption of NVU function can have significant implications for neurovascular health and contribute to the development and progression of neurovascular conditions. Understanding the complex interactions within the NVU is critical for unraveling the pathophysiology of neurovascular conditions and developing novel therapeutic strategies.

Oxidative stress and inflammation processes also play a significant role in the development and progression of neurovascular conditions. It can be caused by an insufficient or interrupted blood supply in blocked or injured blood vessels, which can result in decreased nutrient and oxygen supply to the brain, and subsequent brain damage.

Neurodegenerative Diseases

Neurodegenerative diseases are a group of conditions characterized by the progressive loss of neurons, affecting the function and structure of the brain and the NS.

These diseases can cause a range of symptoms, such as memory loss, difficulty with movement, muscle weakness, seizures, chronic pain, and changes in vision or speech. In addition, the causes of neurological diseases can vary, including genetics, infections, traumatic injury, or environmental factors.

Examples of neurodegenerative diseases are:

• Alzheimer's disease (AD): AD is the most common cause of dementia. It is characterized by an abnormal accumulation of proteins in the brain, which lead to the formation of amyloid plaques and neurofibrillary tangles that disrupt communication between neurons in the brain. Symptoms are memory loss, confusion, and difficulties in decision-making, but they can also be of physical nature, such as difficulties with coordination and movement.
• Parkinson's disease (PD): PD is a condition caused by the degeneration of dopamine-producing cells in the substantia nigra (basal ganglia structure located in the midbrain), which leads to impairment or loss of movement control. Common symptoms of PD are tremors, muscle stiffness, and posture instability.
• Huntington's disease: Huntington’s disease, also known as Huntington’s chorea, is a genetic disorder that results from a mutation in the huntingtin gene, which causes the expression of a toxic protein leading to a progressive deterioration of nerve cells in the brain. Symptoms can include cognitive problems (e.g., difficulties with memory and problem-solving) as well as physical problems such as difficulties with speech and swallowing.
• Amyotrophic lateral sclerosis (ALS): ALS is a progressive neurodegenerative disease that affects nerve cells responsible for controlling voluntary muscles. Affected individuals suffer from symptoms like muscle weakness, paralysis, and eventually respiratory failure.
• Multiple sclerosis (MS): MS is an autoimmune disease that damages the protective insulation of nerve fibers in the brain and spinal cord. The subsequent demyelination of nerves leads to a disrupted electric impulse transmission resulting in symptoms like muscle weakness and difficulties with coordination and balance.

SHSY5Y FUS knockout cells were transfected with a plasmid containing the FUS gene harboring ALS-linked FUS P525L mutation. 48 hours post-transfection, the cells were co-stained for U7 snRNA and FUS. Green: FISH-staining of U7 snRNA. Red: FUS P525L. Blue: Nuclei (DAPI). Cells were stained and imaged in an ibidi Chamber with Coverslip Bottom.
Image Courtesy: Ankur Gadgil, Laboratory of RNA Processing, Center for Advanced Technologies, Uniwersytetu Poznańskiego, Poznań, Poland.

While the exact molecular and cellular mechanisms of neurodegenerative mechanisms are still unknown, they have a progressive impairment and loss of neuron functionality in common. In vitro cell assays like immunofluorescence, tube formation, migration, chemotaxis, and cell culture under flow are valuable methods for studying the underlying mechanisms of neurological conditions in a controlled environment.