Posts Tagged ‘ Neuroscience ’

Cellular Anatomy of the Nervous System

Neuronal Structure

Function of Main Neuronal Components:

  • Soma – The bulbous end of a neuron, containing the cell nucleus. Sometimes referred to as the cell body, it is the ‘control centre’ of the neurone
  • Dendrites – The branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project. They are what receive the input to the neurone.
  • Axon – The slender projection of a nerve cell, or neuron, which conducts electrical impulses away from the neuron’s cell body or soma. They are responsible for sending neurone output to the connecting CNS areas.
  • Axon Hillock – Connects the cell body (the soma) to the axon. This is where action potentials are generated.
  • Myelin Sheath – An electrically insulating material that typically forms a layer around the axon of a neuron. They are able to increase the speed at which action potentials are propagated.
  • Mitochondria – Provide the neurone with chemical energy from respiration.
  • Endoplasmic Reticulum (ER) – Synthesise proteins within the soma.
  • Golgi apparatus – Processes proteins formed by the ER to make them functional, this often includes the process of glycosylation which helps in proper folding of proteins, stability and cell to cell adhesion.
  • Nissl Substance ­- Large granular bodies found in neurons which contain RNA involved in the production of proteins.
  • Microfilaments – The thinnest (actin) filaments of the cytoskeleton found in the cytoplasm of all eukaryotic cells.
  • Neurofilaments – Intermediate sized, protein filaments found specifically in neurons.
  • Microtubules – Microtubules serve as thick, structural components within cells which are also involved in transport.

Identifying Neurones

Bright-field Microscopy & Staining

Golgi Method

The axon and the dendrites of a neurone are too slender and transparent to be seen with normal staining techniques. Golgi’s method stains a limited number of cells at random in their entirety. (The mechanism is still not entirely known). Dendrites, as well as the cell soma, are clearly stained in brown and black and can be followed along their entire length. Enabling the tracking of connections between neurons and making the complex networking structure of many parts of the brain and spinal cord visible.

Nissl Stain

The Nissl stain uses basic aniline to stain RNA blue, and is used to highlight important structural features of neurons. The Nissl substance (rough endoplasmic reticulum) appears dark blue due to the staining of ribosomal RNA, giving the cytoplasm a mottled appearance. Individual granules of extranuclear RNA are named Nissl granules (ribosomes). DNA present in the nucleus stains a similar colour. The cell bodies and proximal dendrites may also be observed.

The Weigert Method

A staining solution of ferric chloride and haematoxylin; myelin stains deep blue, degenerated portions light yellow. This allows the tracking of myelinated fibres.

Immunohistochemical Staining

Immunohistochemical staining involves the use of fluorescent substances to locate specific antigens. A fluorescent ‘tag’ is attached to an antibody, this antibody is then either; directly released onto a substance where it binds to its specific antigen or, an initial antibody binds to the antigen being probed for and the fluorescently tagged antibody then binds to the initial antibody.

Once the antibodies have bound to the antigen, the specific antigen being probed for will then appear to fluoresce under specific light.

Electron Microscopy

Much more powerful than light microscopes, electron microscopes can magnify up to 1,000,000 times. This enables neurone structure to be viewed in very fine detail.

Idealised Neurone Types

The three basic types of idealised neurones include; bipolar, (Pseudo) unipolar and multipolar neurones, their name indicating the number of exits from the soma. Typically these neurones are found in different places around the body:

  • Bipolar – Specialized sensory neurons for the transmission of special senses. As such, they are part of the sensory pathways for smell, sight, taste, hearing and vestibular functions. The most common example are the bipolar neurones found in the retina
  • (Pseudo) Unipolar – Although there appear to be two ends to the unipolar neurone, (such as that observed in the bipolar neurone) there is originally only one exit from the soma, hence the pseudo- often prefixing unipolar. Many types of primary sensory neurones are unipolar.
  • Multipolar – Multipolar neurons constitute the majority of neurons in the brain and include motor neurones and interneurones.

Glial Cells

Glial cells are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for the brain’s neurons. The four main functions of glial cells are to surround neurons and hold them in place, to supply nutrients and oxygen to neurons, to insulate one neuron from another, and to destroy pathogens and remove dead neurons. They also modulate neurotransmission.

Astrocytes

Astrocytes are star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical support of endothelial cells which form the blood-brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a principal role in the repair and scarring process of the brain and spinal cord following traumatic injuries.

It is thought that astrocytes are able to take up glucose from blood vessels and redistribute it to neurones, giving them the nutritional support they require. They can also take up neurotransmitters and ‘detoxify’ them.

Oligodendrocytes

The main function of Oligodendrocytes is the insulation of axons to form Nodes of Ranvier. These nodes are breaks between the insulation of the axon which allow action potentials to jump between them thus increasing the speed of action potential transmission. The speed at which action potentials travel along myelinated axons increases linearly in relation to the diameter. (In unmyelinated axons, speed increases only with the square root of the diameter.)

Microglia

Microglia are a type of glial cells that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defence in the central nervous system (CNS). Microglia are constantly excavating the CNS for damaged neurons, plaques, and infectious agents. The brain and spinal cord are separated from the rest of the body by the blood-brain barrier, which prevents most infections from reaching the vulnerable nervous tissue. In the case where infectious agents are directly introduced to the brain or cross the blood-brain barrier, microglial cells must react quickly to decrease inflammation and destroy the infectious agents before they damage the sensitive neural tissue. Due to the unavailability of antibodies from the rest of the body (few antibodies cross the blood brain barrier due to their large size), microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells. Since this process must be done quickly to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS.

Ependymal Cells

Ependymal cells are epithelial cells that line the cerebrospinal fluid (CSF)-filled ventricles in the brain and the central canal of the spinal cord. Their apical surfaces are covered in a layer of cilia, which circulate CSF around the central nervous system. Their apical surfaces are also covered with microvilli, which absorb CSF. Ependymal cells can also produce CSF.

Meninges, CSF & Venous Drainage

Meninges

The meninges are a group of three membrane layers which wrap around the brain and central nervous system. The meninges consist of three layers (meninx), these include:

  • The Dura Mater
  • The arachnoid membrane
  • The Pia Mater

The primary function of these layers is to protect the central nervous system.

Fig. 1 The meninges surrounding the brain. Meninges of the spinal cord would have another layer between the periosteum and Dura mater – the epidural space and lack the bone layer (skull)

The Dura Mater

The outermost layer of the meninges and therefore closet to the skull is the Dura mater; it is a thick and tough layer composed of dense fibrous tissue which wraps almost entirely around the whole brain and spinal cord. There is little space between the Dura mater layer and the layer below/the bone above it, the exception to this is when (not in the meninges of the spinal cord) the Dura mater splits into two layers forming a gap between them, which is known as the venous sinus. The Dura contains larger blood vessels which split into the capillaries in the pia mater.

In the cranium, the Dura mater also acts as another layer of periosteum, however in the spine there is an epidural space (filled with fat) which separates the Dura mater and periosteum.

The Arachnoid Membrane

The arachnoid layer is much thinner than the Dura mater and contains a lot of underlying space which is filled with CSF (cerebrospinal fluid). This space is known as the subarachnoid space. The arachnoid space is so called because of its spider web-like appearance. It provides a cushioning effect for the central nervous system.

The Pia Mater

This is a very thin and delicate layer which intimately follows the surface of the brain and spinal cord. It is highly vascularised tissue and its capillaries are responsible for nourishing the brain.

Clinical Aspects of the Meninges

The meninges are prone to infection/inflammation – two well-known afflictions associated with the meninges are:

  • Meningitis – This is the inflammation of the meninges surrounding the brain
  • Meningioma – The formation of tumours within the meninges, typically of the Dura mater

Cerebrospinal Fluid

Cerebrospinal fluid (CSF) is a clear, saline bodily fluid that occupies the subarachnoid space and the ventricular system around and inside the brain. It is produced continuously at a steady rate and is essential for the normal functioning of the CNS. There is very little protein and virtually no cells present in normal CSF, only around 35mg per 100ml compared to 7,000mg per 100ml in typical serum. It is therefore a greater proportion of water (99%) compared to 93% in serum.

Production

CSF is produced in the brain by modified ependymal cells in the vascular choroid plexus (approx. 50-70%), and the remainder is formed around blood vessels and along ventricular walls. Both filtration and secretion occurs by epithelial cells.

Flow

Generally CSF flows from the lateral ventricles, through the foramina of Monroe to the 3rd ventricle, then through the cerebral aqueduct (of Sylvius) to the 4th ventricle. It then mostly flows out of the lateral foramen of Luschka and into the cisterna magna (a dilation of the subarachnoid space), or caudally into the central canal of the spinal cord.

Exit/Drainage

Generally CSF will exit via the arachnoid villi. There are other possible routes of drainage however; such as absorption by venules in the pia mater, through spinal veins and lymphatics (around the roots of the spinal nerves) and by direct venous drainage from the subarachnoid space into the venous sinuses.

Sampling

CSF can be sampled from an organism by cisternal puncture. The CSF should flow into the container without the need to draw it in, due to pressure. No more than a maximum of 1ml per 5kg of body tissue should be extracted.

Things to look out for in the CSF sample include:

  • Colour – Red/Yellow staining of the normally clear fluid could indicate a haemorrhage. (Poor technique may also cause some blood to be extracted with the CSF however)
  • Protein content – If an increase in protein content is observed, this can act as a nonspecific indicator of CNS disease
  • Chemical content – A decrease in CSF glucose may indicate bacterial or fungal meningitis
  • Cell count – CSF cell count is usually low, a cloudy appearance may indicate higher cell counts which could be a sign of CNS disease

Venous Drainage

Cranial Venous Drainage

The brain and spinal cord use a series of dural sinuses, in addition to veins to remove CSF and venous blood. Dural sinuses have no valves, (the venous system of the cranium generally has few valves).

Spinal Venous drainage

A similar system exists to drain venous blood from the spinal cord. There is a direct continuity with the cranial sinuses. CSF and venous blood drain via intervertebral veins into either the vertebral, azygos veins or the vena cava.