Posts Tagged ‘CNS’

New virus isolated from patients with severe brain infections

Researchers have identified a new virus in patients with severe brain infections in Vietnam. Further research is needed to determine whether the virus is responsible for the symptoms of disease.

The virus was found in a total of 28 out of 644 patients with severe brain infections in the study, corresponding to around 4%, but not in any of the 122 patients with non-infectious brain disorders that were tested.

Infections of the brain and central nervous system are often fatal and patients who do survive, often young children and young adults, are left severely disabled. Brain infections can be caused by a range of bacterial, parasitic, fungal and viral agents, however, doctors fail to find the cause of the infection in more than half of cases despite extensive diagnostic efforts. Not knowing the causes of these brain infections makes public health and treatment interventions impossible.

Researchers at the Oxford University Clinical Research Unit, Wellcome Trust South East Asia Major Overseas Programme and the Academic Medical Center, University of Amsterdam identified the virus, tentatively named CyCV-VN, in the fluid around the brain of two patients with brain infections of unknown cause. The virus was subsequently detected in an additional 26 out of 642 patients with brain infections of known and unknown causes.

Using next-generation gene sequencing techniques, the team sequenced the entire genetic material of the virus, confirming that it represents a new species that has not been isolated before. They found that it belongs to a family of viruses called the Circoviridae, which have previously only been associated with disease in animals, including birds and pigs.

Dr Rogier van Doorn, Head of Emerging Infections at the Wellcome Trust Vietnam Research Programme and Oxford University Clinical Research Unit Hospital for Tropical Diseases in Vietnam, explains: “We don’t yet know whether this virus is responsible for causing the serious brain infections we see in these patients, but finding an infectious agent like this in a normally sterile environment like the fluid around the brain is extremely important. We need to understand the potential threat of this virus to human and animal health.”

The researchers were not able to detect CyCV-VN in blood samples from the patients but it was present in 8 out of 188 fecal samples from healthy children. The virus was also detected in more than half of fecal samples from chickens and pigs taken from the local area of one of the patients from whom the virus was initially isolated, which may suggest an animal source of infection.

Dr Le Van Tan, Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, said: “The evidence so far seems to suggest that CyCV-VN may have crossed into humans from animals, another example of a potential zoonotic infection. However, detecting the virus in human samples is not in itself sufficient evidence to prove that the virus is causing disease, particularly since the virus could also be detected in patients with other known viral or bacterial causes of brain infection. While detection of this virus in the fluid around the brain is certainly remarkable, it could still be that it doesn’t cause any harm. Clearly we need to do more work to understand the role this virus may play in these severe infections.”

The researchers are currently trying to grow the virus in the laboratory using cell culture techniques in order to develop a blood assay to test for antibody responses in patient samples, which would indicate that the patients had mounted an immune response against the virus. Such a test could also be used to study how many people in the population have been exposed to CyCV-VN without showing symptoms of disease.

The team are collaborating with scientists across South East Asia and in the Netherlands to determine whether CyCV-VN can be detected in patient samples from other countries and better understand its geographical distribution.

Professor Menno de Jong, head of the Department of Medical Microbiology of the Academic Medical Centre in Amsterdam said: “Our research shows the importance of continuing efforts to find novel causes of important infectious diseases and the strength of current technology in aid of these efforts.”

Journal reference: L.V. Tan et al . Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections. mBio, June 2013. DOI: 10.1128/mBio.00231-13

The above story is reprinted from materials provided by Wellcome Trust, via MedicalXpress.


The Bacteria That Make Insects Eat Their Own Brains

September 5, 2012 Leave a comment

As far as bacteria are concerned, other living creatures are just another niche to exploit, which means that pretty much every animal and plant has a set of bacterial pathogens that come along with it. These bacteria have made the animal in question their speciality, and are highly adapted to live inside their hosts. While these bacteria often make the host ill, or less fit, or sometimes dead, the longer they live with their host, overall, the less they damage it. After all, it’s no help to the bacteria if their home drops down dead right after they’ve moved in.

A great example of this appeared in PLoS Pathogens this month (reference 1), concerning the bacteria Wolbachia. These bacteria infect insects and other arthropods and are much beloved of journalists (well, compared to other insect bacteria at least) because one of their effects is to stop insects producing male offspring (so only female survive to pass on the bacterial genome), which gives journalists the opportunity to write silly headlines.

An electron micrograph of an insect cell, with three Wolbachia bacteria inside (the large circular blobs with white lines surrounding them). Image from reference 2. (up)

As well as passing from females onto their offspring, Wolbachia can also be transmitted horizontally, that is between insects in the same generation. In its normal host the Wolbachia is not hugely damaging (apart from removing all males from the population) but when transmitted to a new species it causes various unpleasant nervous system complications, often leading to death. Clearly, the bacteria are more virulent when they encounter a new species. However when the bacterial infection was closely examined, it was found that infected individuals of both species contained the same number of bacteria. It wasn’t just that the new species couldn’t respond to the infection, it was in fact the way they responded that was doing the damage.

As it turns out, the reason Wolbachia are more dangerous in new species isn’t because the bacteria go wild in the unexplored territory, rather it’s because the new host doesn’t know how to deal with them. The insects that are used to dealing with the presence of the bacteria have developed ways to contain the infection, or just tolerate it. New species however, tend to panic, particularly as the bacteria tend to congregate in the gonads (sex organs) and the central nervous system, which even insects understand are bad places to have bacteria.

As the bacteria are found inside cells, the best way for an insect immune system to get rid of them, is by destroying the cells that house the bacteria. Which, as previously mentioned, are mainly the gonads and the central nervous system. When the Wolbachia get into a new species, the first response of the insect is to quickly and efficiently destroy any cells which have bacteria inside them. As a consequence the unfortunate insect basically destroys its own brain, leading to various unpleasant symptoms and death.

The carpenter ant, Camponotus pennsylvanicus. Many species of Camponotus are infected with Wolbachia. Image from reference 3. (up)

Even in insects, the immune system is vital to defend animals from bacterial, fungal, and viral attacks. However it’s fascinating to see the cases where the immune system (even ‘primitave’ immune systems that consist of nothing more than infected cells quickly being removed) can lead to issues by over-reacting to a threat. The best response to the Wolbachia is for the insects to learn to deal with it, rather than to attempt to launch counter-attacks which can be damaging for the animal as a whole.


Adopted from: Rat Lab blog

1: Le Clec’h W, Braquart-Varnier C, Raimond M, Ferdy JB, Bouchon D, & Sicard M (2012). High virulence of wolbachia after host switching: when autophagy hurts. PLoS pathogens, 8 (8) PMID22876183

2: (2004) Genome Sequence of the Intracellular Bacterium Wolbachia. PLoS Biol 2(3): e76. doi:10.1371/journal.pbio.0020076

3: Wernegreen JJ (2004) Endosymbiosis: Lessons in Conflict Resolution. PLoS Biol 2(3): e68. doi:10.1371/journal.pbio.0020068




The Reticular Formation, Limbic System and Basal Ganglia

February 19, 2012 2 comments

The Reticular Formation

It’s a ‘diffuse net’ which is formed by nerve cells and fibers. It extends from the neuroaxis spinal cord through medulla, pons, midbrain, subthalamus, hypothalamus and thalamus (spinal cord is relayed superiorly to the cerebral cortex).

Many afferent and efferent pathways project in and out of the RF from most parts of the CNS. The main pathways through the RF is poorly defined and difficult to trace using silver stains. Reticular formation can be divided into three columns : median, medial and lateral columns.

Functions of the Reticular formation

1.   Control of skeletal muscles:

  • RF modulates muscle tone and reflex activities (via reticulospinal and reticulo bulbar tracts). It is important in controlling muscles of facial expression when associated with emotions.

2.   Control somatic and visceral sensation (influence can be excitatory or inhibitory)

3.   Control of autonomic nervous system

4.   Control of endocrine nervous system (hypothalamus and the pituitary)

5.   Influence on the biological clock (rhythm)

6.   The reticular activating system (arousal and level of consciousness are controlled by the RF)

Clinical note

When a person smiles for a joke, the motor control is provided by the RF on both side of the brain. The fibers from RF is separated from corticobulbar pathway (supply for facial muscles). If a patient suffers a stroke that involves corticobulbar fibers, he or she has facial paralysis on the lower part of the face, but is still able to smile symmetrically.

The Limbic System

 Limbic structures   Functions of the limbic system 
  1. Sub callosal, cingulated and parahippocampal gyri
  2. Hippocampal formation
  3. Amygdaloid nucleus
  4. Mammillary bodies
  5. Anterior thalamic nucleus
1. Influence the emotional behavior:a. Reaction to fear and angerb. Emotions associated with sexual behavior

2. Hippocampus is involved in converting short term memory to long term memory (If the hippocampus is damaged, patient is unable to store long term memory – Anterograde amnesia)

The  Basal Ganglia and their connections

Connections of the Basal Ganglia

Yellow arrow : Pallidofugal fibers

Caudate nucleus and the Putamen: main sites of receiving inputs

Globus pallidus: main site from which output leaves

Afferent and Efferent fibers

Connections of the caudate nucleus and Putamen Connections of the Globus pallidus
Afferent Efferent Afferent Efferent
CS: CorticostriateTS: Thalamostriate

NS: Nigrostriate

BS: Brainstem striatal fibers

SP: Striatopallidalfibers

SN: Striatonigral fibers

SP: Striatopallidalfibers Pallidofugalfibers

Functions of  the Basal Nuclei

Basal Nuclei controls muscular movements by influencing the cerebral cortex (it doesn’t have direct control through descending pathways to the brainstem and spinal cord). It helps to prepare for the movements (enables the trunk and limbs to be placed in appropriate positions before discrete movements of the hands and feet).

Functional connections of the Basal Nuclei and how they influence muscle activities

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5. Dale Purves Neuroscience, 3rd Edition
6. Suzan Standring Gray’s Anatomy
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