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The spinal cord is the communication gateway between the brain and spinal nerves, which innervate the trunk and limbs. The cord is a long, thin tube of nervous tissue, enclosed in 3 membranes of the meninges which, in turn, are protected within the bones of the vertebral column. The 31 pairs of spinal nerves arise from the cord and emerge from the vertebrae. The spinal cord extends from the brainstem to the level of upper lumbar vertebrae. In the lower lumbar and sacral regions, nerve roots descend within the spinal canal before exiting, forming the cauda equina.

In cross section, two types of nervous tissue can be seen in the cord: a butterfly-shaped central core of gray matter, and a surrounding white matter. The gray matter contains cell bodies and dendrites of neurons. This is where neurons synapse and transmit information to each other. The white matter, on the other hand, is made of bundles of axons, and serves to conduct information up and down the cord. These bundles are organized into specific groups with specific functions, forming the so-called spinal tracts. Spinal tracts are essentially high-speed cables, each carries a certain type of information, in a one-way traffic, between the spinal cord and a certain area in the brain. All tracts occur on both sides, left and right, of the cord. Ascending tracts conduct sensory information up to the brain, while descending tracts convey motor instructions down the cord. Some tracts cross over to the other side of the cord, before they reach the brain. They convey sensory information from one side of the body to the other side of the brain. When this happens, the information is said to be transmitted contralaterally. Tracts that stay on the same side all the way are said to conduct information ipsilaterally.

Spinal nerves are mixed nerves, they contain both sensory and motor fibers. These fibers are separated shortly before they reach the spinal cord. Sensory fibers enter the cord via the dorsal root, while motor fibers exit via the ventral root.

A sensory pathway typically involves 3 neurons:

– First-order neurons detect stimuli and transmit signals to the spinal cord. The axons of these neurons form sensory fibers that enter the cord via the dorsal root of spinal nerve.

– Inside the cord, first-order neurons synapse with second-order neurons, which ascend a specific tract to the brainstem, or further up to the thalamus. In some pathways, first-order neurons ascend the tract to the brainstem, where they synapse with second-order neurons, which continue to the thalamus.

– Third-order neurons conduct the information the rest of the way to the sensory cortex.

A motor pathway usually involves 2 neurons: an upper motor neuron starts in the motor cortex or brainstem, and a lower motor neuron continues from the brainstem or spinal cord. They conduct motor instructions down, along a specific descending tract. The axons of lower motor neurons exit the cord via the ventral root of spinal nerve, where they continue as motor fibers to effector organs.

The spinal cord is also responsible for fast, involuntary responses of skeletal muscles, called somatic reflexes. Reflexes are essentially automatic and do not require input from the brain, although the brain is informed and aware, usually after-the-fact. A somatic reflex involves a reflex arc composed of a somatic receptor, a sensory neuron, an interneuron, a motor neuron, and an effector muscle. Some reflexes are however more complex, and require multiple pathways, as well as central coordination from the brain. For example, when someone steps on something sharp and lifts their injured leg, the other leg also must react to keep balance or the person would fall over. This involves multiple muscles and require contralateral pathways at several levels of the cord, as well as movement coordination from the brain.

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The function of the nervous system is to provide rapid communication and integration between various organs, as well as with the outside environment. It detects changes within the body and in its surroundings, and responds accordingly. Fast communication is achieved by means of electrical signals, known as nerve impulses, which are generated and carried by specialized cells, called neurons.
The major components of the nervous system are the brain, spinal cord and nerves. The brain, enclosed and protected in the cranium, is the central processing center. It receives information, makes decision and coordinates the body response. The spinal cord, enclosed in the spinal column, functions as a communication gateway between the brain and the trunk and limbs. Nerves are cordlike structures that conduct information, similar to electricity-conducting wires. They are composed of axons of neurons, the cell bodies of which are clustered in knot-like structures called ganglia. Ganglia commonly serve as relay centers, where neurons synapse and transmit information to each other.
The brain and spinal cord make up the central nervous system, while nerves and ganglia constitute the peripheral nervous system.
Functionally, a nerve fiber can be sensory or motor. Sensory nerve fibers carry sensory information from sensory receptors to the central nervous system, while motor nerves conduct motor instructions from the central nervous system to effector organs – the muscles and glands. Nerves that contain both sensory and motor fibers are known as mixed nerves.
There are 2 major groups of nerves: cranial nerves and spinal nerves:
– The 12 pairs of cranial nerves emerge from the base of the brain and relay information between the brain and the head and neck regions. The cranial nerve X, named vagus nerve, also communicates with internal organs.
– The 31 pairs of spinal nerves arise from segments of the spinal cord and innervate the trunk and limbs. Spinal nerves communicate with the brain via the spinal cord. All spinal nerves are mixed nerves, they contain both sensory and motor fibers. Typically, sensory receptors send impulses by way of sensory fibers in spinal nerves, to the spinal cord, which relays the information up to the brain. The brain interprets the information and sends back instructions, down the spinal cord, to motor fibers in spinal nerves, to reach effector organs.
The peripheral nervous system can be divided into somatic and visceral subdivisions. The somatic nervous system includes sensory nerves from the skin, muscles, bones and joints; and motor nerves that innervate skeletal muscles. This system controls voluntary muscular contractions, as well as involuntary somatic reflexes. The visceral nervous system, on the other hand, includes sensory division that detects changes in the viscera – the organs in the thoracic and abdominal cavities; and motor division that controls cardiac muscle, smooth muscle of internal organs and glands. It produces, for example, faster heart rate and breathing rate during physical exercise, and slower cardiorespiratory rate during sleep. The visceral motor division is also known as the autonomic nervous system because it is largely autonomous, acting independently of the body’s consciousness and voluntary control.

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The blood-brain barrier refers to the highly selective permeability of blood vessels within the central nervous system. The barrier controls, in a precise manner, substances that can enter or leave the nervous tissue. It helps maintain the stable state, or homeostasis, of brain tissue, amid the fluctuations of circulating substances in the blood, many of which can act as neurotransmitters and could create chaos in neuronal activities if allowed to diffuse freely into the brain. The barrier also protects the brain from blood-borne pathogens and toxins.
The blood-brain barrier is composed of several cell types, including:
– Endothelial cells that form the wall of blood vessels;
– Mural cells, namely pericytes, partially covering the outside of endothelial cells;
– And glial cells astrocytes, whose extended processes, called end-feet, wrap around the vessels.
The endothelial cells alone can fulfill the functions of the blood-brain barrier, but their interactions with the adjacent cells seem to be required for its formation, maintenance and regulation.
The brain endothelial cells, unlike their counterparts in other tissues, possess unique properties that allow them to tightly control the passage of substances between the blood and brain. These properties can be classified into physical, transport, and metabolic categories:
– The brain endothelial cells are held together by tight junctions, which serve as physical barriers, preventing movements of substances through the space between cells.
– They have very low rates of vesicle-mediated transcellular transport.
– They control the movement of ions and substances with specific transporters, of which there are two major types: efflux transporters and nutrient transporters:
+ Efflux transporters use cellular energy to move substances against their concentration gradient. These transporters are usually located on the blood side of endothelial cells. They transport lipophilic molecules, which have passively diffused through the cell membrane, back to the blood.
+ Nutrient transporters, on the other hand, facilitate the movement of nutrients, such as glucose and essential amino acids, into the brain, down their concentration gradient.
– The brain endothelial cells also contains a number of enzymes that metabolize, and thus inactivate, certain neurotransmitters, drugs and toxins, preventing them from entering the brain.
An intact blood-brain barrier is critical for normal brain functions. Neurological diseases such as encephalitis, multiple sclerosis, brain traumas, Alzheimer’s disease, epilepsy, strokes and tumors, can breach the barrier, and this, in turn, contributes to disease pathology and further progression.
To note, however, that not all areas of the brain have the blood-brain barrier. For example, some brain structures are involved in hormonal control and require better access to systemic blood, so they can detect changes in circulating signals and respond accordingly. These non-barrier areas are located around the midline of the ventricular system, and are known as circumventricular organs. Some of their bordering regions have a leaky barrier.
The blood-brain barrier also has its downside. While it protects the brain from unwanted drugs and toxins, it also prevents therapeutic drugs from entering the central nervous system to treat diseases. Several strategies are developed to overcome this obstacle, including:
– delivering the drug directly into the cerebrospinal fluid;
– use of vasoactive compounds;
– designing drugs with higher lipid solubility;
– hacking the endogenous transport system to carry the drug,
– and blocking the efflux transporter that pumps the drug back to the bloodstream.

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Food intake and energy expenditure must be balanced to maintain a healthy body weight. This balance is kept by the central nervous system, which controls feeding behavior and energy metabolism.
Several brain systems are involved, including the brainstem which receives neuronal inputs from the digestive tract, and the hypothalamus which picks up hormonal and nutritional signals from the circulation. These two systems collect information about the body’s nutrient status and respond accordingly. They also interact with the reward and motivation pathways, which drive food-seeking behavior.
The arcuate nucleus, ARC, of the hypothalamus, emerges as the major control center. There are two groups of neurons, with opposing functions, in the ARC: the appetite-stimulating neurons expressing NPY and AGRP peptides, and the appetite-suppressing neurons producing POMC peptide.
Appetite-stimulating neurons are activated by hunger, while appetite-suppressing neurons are stimulated by satiety, or fullness.
Neurons of the ARC project to other nuclei of the hypothalamus, of which the paraventricular nucleus, PVN, is most important. PVN neurons further process the information and project to other circuits outside the hypothalamus, thus coordinating a response that controls energy intake and expenditure.
Short-term regulation of feeding is based on how empty or how full the stomach is, and if there are nutrients in the intestine. In the fasting state, an empty stomach sends stretch information to the brainstem, signaling hunger. It also produces a peptide called ghrelin, which acts on the arcuate nucleus to stimulate feeding. Ghrelin also acts directly on the PVN to reduce energy expenditure.
Upon food ingestion, distension of the stomach is perceived by the brainstem as satiety. Ghrelin is no longer produced. Instead, several other gut peptides are released from the intestine and act on the hypothalamus and other brain areas to suppress appetite and increase energy expenditure.
Long-term regulation, on the other hand, takes cues from the amount of body fat: low body fat content encourages feeding and energy preservation, while high body fat suppresses appetite and promotes energy expenditure. Two hormones are involved: leptin and insulin.
Insulin is a hormone produced by the pancreas and is released into the bloodstream upon food ingestion, when blood glucose starts to rise. Leptin is a hormone secreted by adipose tissues in a process dependent on insulin. The amount of circulating leptin in the plasma is directly proportional to the body fat content. Increased leptin levels in the blood signal to the brain that the body has enough energy storage, and that it has to stop eating and burn more energy. Leptin and insulin seem to work together on hypothalamic nuclei, as well as other brain areas, to inhibit food intake and increase energy expenditure.
Obesity results from the dysregulation of feeding behaviors and energy metabolism. Obesity is most commonly associated with chronic low leptin activities, which trick the brain into thinking that the body is always starved. This leads to overeating and excessive energy storage as fats.
Both genetic and lifestyle factors contribute to low leptin signaling, but the contribution of each factor varies widely from person to person.
The major lifestyle factor is a high-fat, energy-rich diet. In an early stage of high-fat-diet–induced obesity, increased amounts of saturated fatty acids cross the blood brain barrier and provoke an inflammatory response in hypothalamic neurons. Inflammation induces stress in these neurons, blunting their response to leptin. This is known as leptin resistance. Leptin levels are high, but because the cells cannot react to leptin, the brain interprets it as low and triggers the starvation response.
Genetic factors include mutations in the leptin gene itself, or in one of the numerous downstream genes that are required for leptin action in various pathways. Leptin deficiency due to gene mutations is very rare. More common are mutations in the downstream genes, which render a certain pathway irresponsive to leptin.
A major risk factor for childhood obesity is maternal obesity and mother’s high-fat-diet during pregnancy and lactation. A maternal diet rich in saturated fats can cause inflammation in the infant’s hypothalamus. It may also prime the reward pathways in infants, influencing their food choice toward energy-rich foods.