Plasticity of brain

                       
                        Neuroplasticity


Causes of Brain Damage

six causes of brain damage: brain tumors, cerebrovascular disorders, closed head injuries, infections of the brain, neurotoxins, and genetic factors.

Brain Tumors

A tumor, or neoplasm (literally, “new growth”), is a mass of cells that grows independently of the rest of the body.

About 20 percent of tumors found in the human brain are meningiomas tumors that grow between the meninges, the three membranes that cover the central nervous system.

All meningiomas are encapsulated tumors—tumors that grow within their own membrane.

As a result, they are particularly easy to identify on a CT scan, they can influence the function of the brain only by the pressure they exert on surrounding tissue, and they are almost

always benign tumors—tumors that are surgically removable with little risk of further growth in the body

Infiltrating tumors are those that grow diffusely through surrounding tissue.

As a result, they are usually malignant tumors; that is, it is difficult to remove or destroy them completely, and any cancerous tissue that remains after surgery continues to grow.

 Gliomas (brain tumors that develop from glial cells) are infiltrating, rapidly growing, and unfortunately common

About 10 percent of brain tumors do not originate in the brain. They grow from infiltrating cells that are carried
to the brain by the bloodstream from some other part of the body. These tumors are called metastatic tumors
(metastasis refers to the transmission of disease from one organ to another)

acoustic neuromas (neuromas are tumors that grow on nerves or tracts).


Cerebrovascular Disorders: Strokes

Strokes are sudden-onset cerebrovascular disorders that cause brain damage.

The area of dead or dying tissue produced by a stroke is called an infarct. Surrounding the infarct is a dysfunctional area called the penumbra.

The tissue in the penumbra may recover or die in the ensuing days, depending on a variety of factors. The primary goal of treatment following stroke is to save the penumbra.


There are two major types of strokes: those resulting from cerebral hemorrhage and those resulting from cerebral ischemia

Cerebral hemorrhage (bleeding in the brain) occurs when a cerebral blood vessel ruptures and blood seeps into the surrounding neural tissue and damages it. Bursting aneurysms are a common cause of intracerebral hemorrhage. An aneurysm is a pathological balloon like dilation that forms in the wall of an artery at a point where the elasticity of the artery wall is defective

Cerebral ischemia is a disruption of the blood supply to an area of the brain. Ischemia-induced brain damage has two important properties.

  First, it takes a while to develop
   
  Second, ischemia-induced brain damage does not occur equally in all parts of the brain—particularly susceptible are neurons in certain areas of the hippocampus

glutamate, the brain’s most prevalent excitatory neurotransmitter, plays a major role in ischemiainduced
brain damage


Closed-Head Injuries

Brain injuries produced by blows that do not penetrate the skull are called closed-head injuries

Contusions are closed-head injuries that involve damage to the cerebral circulatory system. Such damage
produces internal hemorrhaging, which results in a hematoma

 A hematoma is a localized collection of clotted blood in an organ or tissue

contusions frequently occur on the side of the brain opposite the side struck by a blow. The reason for such
so-called contrecoup injuries is that the blow causes the brain to strike the inside of the skull on the other
side of the head.

When there is a disturbance of consciousness following a blow to the head and there is no evidence of
a contusion or other structural damage, the diagnosis is concussion.

Infections of the Brain

two different types of infections of the brain.

An invasion of the brain by microorganisms is a brain infection, and the resulting inflammation is called encephalitis

There are two common types of brain infections: bacterial infections and viral infections.

Bacterial infection. When bacteria infect the brain, they often lead to the formation of cerebral abscesses— pockets of pus in the brain. Bacteria are also the major cause of meningitis

Syphilis is one bacterial brain infection  Syphilis bacteria are passed from infected to noninfected individuals through contact with genital sores. The infecting bacteria then go into a dormant stage for several years before they become virulent and attack many parts of the body, including the brain. The syndrome of mental illness and dementia that results from a syphilitic infection is called general paresis.

Viral Infection There are two types of viral infections of the nervous system: those that have a particular affinity for neural tissue and those that attack neural tissue but have no greater affinity for it than for other tissues.


Neurotoxins

The nervous system can be damaged by exposure to any one of a variety of toxic chemicals, which can enter general circulation can accumulate in the brain and permanently damage it, producing a toxic psychosis (chronic mental illness produced by a neurotoxin).

Tardive dyskinesia (TD)—Its primary symptoms are involuntary smacking and sucking movements of the lips, thrusting and rolling of the tongue, lateral jaw movements, and puffing of the cheeks.

Some neurotoxins are endogenous (produced by the patient’s own body).

Genetic Factors

Some neuropsychological diseases of genetic origin are caused by abnormal recessive genes that are passed from parent to offspring. Ex. Down syndrome

Programmed Cell Death

that neurons and other cells have genetic programs for destroying themselves by a process
called apoptosis Apoptosis plays a critical role in early development by eliminating extra neurons. It also plays a role in brain damage

necrosis is passive cell death resulting from injury


Neurological Diseases

 This module considers five diseases associated with brain damage: epilepsy, Parkinson’s disease, Huntington’s
disease, multiple sclerosis, and Alzheimer’s disease.

Epilepsy

The primary symptom of epilepsy is the epileptic seizure,

Some epileptics experience peculiar psychological changes just before a seizure. These changes, called epileptic auras, may take many different forms—for example, a bad smell, a specific thought, a vague feeling of familiarity, a hallucination

Epileptic auras are important for two reasons. First, the nature of the auras provides clues concerning the location of the epileptic focus. Second, epileptic auras can warn the patient of an impending convulsion

the type of seizures two general categories—focal seizures or generalized
seizures



FOCAl  SeIzureS. A focal seizure is a seizure that does
not involve the entire brain. There are two major categories of focal seizures: simple partial seizures and complex partial seizures.

 Simple partial seizures are focal seizures whose symptoms are primarily sensory or motor or both; they are sometimes called Jacksonian seizures

complex partial seizures are often restricted to the temporal lobes, and those who experience
them are often said to have temporal lobe epilepsy.

During a complex partial seizure, the patient engages in compulsive, repetitive, simple behaviors commonly referred to as automatisms

Generalised SeIzureS. Generalized seizures involve the entire brain.

generalized seizures occur in many forms. One is the tonic-clonic seizure.
The primary symptoms of a tonic-clonic seizure are loss of consciousness, loss of equilibrium, and a violent tonic-clonic convulsion—a convulsion involving both tonus and clonus. Tongue biting, urinary incontinence, and cyanosis (turning blue from excessive extraction of oxygen from the blood during the convulsion) are common manifestations of tonic-clonic convulsions.

The hypoxia (shortage of oxygen supply to a tissue, for example, to the brain) that accompanies a tonic clonic seizure can itself cause brain damage.

A second type of generalized seizure is the absence seizure. Absence seizures are not associated with convulsions;
their primary behavioral symptom is a disruption of consciousness associated with a cessation of ongoing behaviour a vacant look, and sometimes fluttering eyelids.


Parkinson’s Disease

Parkinson’s disease is a movement disorder of middle and old age

The most common symptoms of the fullblown disorder are a tremor that is pronounced during inactivity but not during voluntary movement or sleep, muscular rigidity, difficulty initiating movement, slowness of movement, and a masklike face.

Although Parkinson’s patients often display cognitive deficits, dementia is not always associated with the disorder

Parkinson’s disease is associated with widespread degeneration, but it is particularly severe in the substantia Nigra

Autopsy often reveals clumps of proteins in the surviving dopaminergic neurons of the substantia nigra—the clumps are called lewy bodies,

the symptoms of Parkinson’s disease can be alleviated by injections of L-dopa— the chemical from which the body synthesizes dopamine.

One of the more controversial treatments for Parkinson’s disease  is deep brain stimulation a treatment in which low-intensity electrical stimulation is continually applied to an area of the brain through a stereotaxically implanted electrode


Huntington’s Disease

Huntington’s disease is a progressive motor disorder, but, unlike Parkinson’s disease, it is rare (1 in 10,000), it has a simple genetic basis,  is always associated with severe dementia.

The first clinical sign of Huntington’s disease is often increased fidgetiness. As the disorder develops, rapid, complex, jerky movements of entire limbs (rather than individual muscles) begin to predominate. Eventually, motor and intellectual deterioration become  severe

There is no cure; death typically occurs about 15 years after the appearance of the first symptoms.

Huntington’s disease is passed from generation to generation by a single mutated dominant gene, called huntingtin The protein it codes for is known as the huntingtin protein


Multiple Sclerosis

Multiple sclerosis (MS) is a progressive disease that attacks the myelin of axons in the CNS.

it typically attacks people in their early adulthood. First, there are microscopic areas of degeneration on myelin sheaths but eventually damage to the myelin is so severe that the associated axons become dysfunctional and degenerate Ultimately, many areas of hard scar tissue develop in the CNS (sclerosis means “hardening”).

Multiple sclerosis is often considered to be an autoimmune disorder—a disorder in which the body’s immune system attacks part of the body as if it were a foreign substance. In multiple sclerosis, myelin is the focus of the faulty immune reaction.

However, it should be noted that in multiple sclerosis, damage to axons and neurons occurs even without demyelination

Common symptoms of advanced multiple sclerosis are visual disturbances, muscular weakness, numbness, tremor, and ataxia (loss of motor coordination). In addition, cognitive deficits and emotional changes occur in some patients

Epidemiology is the study of the various factors such as diet, geographic location, age, gender, and race that influence the distribution of a disease in the general population.

Risk factors for multiple sclerosis.
The most well-established ones include vitamin Ddeficiency, exposure to the Epstein-Barr virus (the most common cause of mononucleosis), and cigarette smoking


Alzheimer’s Disease

Alzheimer’s disease is the most common cause of dementia in the elderly

Alzheimer’s disease is progressive.

Its early stages are often characterized by a selective decline in memory, deficits in attention, and personality changes;

 its intermediate stages are marked by confusion, irritability, anxiety,and deterioration of speech; and in

 its advanced stages, the patient deteriorates to the point that even simple responsessuch as swallowing and bladder control are difficult.

Alzheimer’s disease is terminal


the pathogenic spread hypothesis. The pathogenic spread hypothesis proposes that many common neurodegenerative diseases (e.g., Alzheimer’s disease,Parkinson’s disease) result from the presence of misfolded proteins that initiate a chain reaction wherein they cause other proteins to misfold.


Kindling Model of Epilepsy

The progressive development and intensification of convulsions elicited by a series of periodic brain stimulations became known as the kindling phenomenon

There are two main features of kindling,.:
 The first is that the neuroplastic changes underlying kindling are permanent.
The second is that kindling is produced by distributed, asopposed to massed, stimulations

Transgenic refers to animals into which genes of another species have been introduced



Responses to Nervous System Damage: Degeneration, Regeneration, Reorganization, and Recovery


Neural Degeneration

Neural degeneration (neural deterioration and death) is a component of both brain development and disease. Neural degeneration, as it typically occurs, is a complex process:
It is greatly influenced by nearby glial cells , by the activity of the degenerating neurons, and by the particular cause of the degeneration

Two kinds of neural degeneration ensue: anterograde degeneration and retrograde degeneration.

Anterograde degeneration is the degeneration of the distal segment—the segment of a cut axon from the cut to the synaptic terminals

retrograde degeneration is the degeneration of the proximal segment—the segment of a cut axon from the cut back to the cell body


Sometimes, degeneration spreads from damaged neurons to neurons that are linked to them by synapses; this is called transneuronal degeneration.

In some cases, transneuronal degeneration spreads from damaged neurons to the neurons on which they synapse; this is called anterograde transneuronal degeneration.

And in some cases  it spreads from damaged neurons to the neurons that synapse on them; this is called retrograde transneuronal degeneration.




Neural Regeneration

Neural regeneration—the re-growth of damaged neurons does not proceed as successfully in mammals and other higher vertebrates as it does in most invertebrates and lower vertebrates

Regeneration is virtually nonexistent in the CNS of adult mammals and is at best a hit-or-miss affair in the PNS.

In the mammalian PNS, regrowth from the proximal damaged nerve usually begins 2 or 3 days after axonal damage, once new growth cones have formed What happens next depends on the nature of the injury;

there are three possibilities.:
1. if the original Schwann cell myelin sheaths remain intact, the regenerating peripheral axons grow through them to their original targets at a rate of a few millimetres per day.

2.  if the peripheral nerve is severed and the cut ends become separated by a few millimeters, regenerating axon tips often grow into incorrect sheaths and are guided by them to incorrect destinations

3. third, if the cut ends of a severed mammalian peripheral nerve become widely separated or if a lengthy section of the nerve is damaged, there may be no meaningful regeneration at all


Why do mammalian PNS neurons regenerate but mammalian CNS neurons normally do not?

Schwann cells, which myelinate PNS axons, clear the debris and scar tissue resulting from neural degeneration and promote regeneration in the mammalian PNS by producing both neurotrophic factors and celladhesion molecules (CAMs).

In contrast, oligodendroglia, which myelinate CNS axons, do not clear debris or stimulate or guide regeneration; indeed, they release factors that actively block regeneration
Moreover, in the CNS, astrocytes form a glial scar after injury that presents a physical barrier to axonal regrowth and also actively releases inhibitors of axonal growth

When an axon degenerates, axon branches grow out from adjacent healthy axons and synapse at the sites vacated by the degenerating axon; this is called collateral sprouting.



Neural Reorganization
Adult mammalian brains have the ability to reorganize themselves in response to experience.  they can also reorganize themselves in response to damage.

MECHANISMS OF NEURAl  REORGANIZATION.:

Two kinds of mechanisms have been proposed to account for the reorganization
of neural circuits: a strengthening of existing connections, possibly through release from inhibition, and the establishment of new connections by collateral sprouting


Recovery of Function after CNS Damage
it is clear that recovery is most likely when lesions are small and patients are young Cognitive reserve (roughly equivalent to education and intelligence) is thought to play a role in the improvements observed after brain damage that do not result from true recovery of brain function. Cognitive reserve has also been used to explain why highly educated people are less susceptible to the effects of brain deterioration associated with aging