Posts tagged CNS

The nervous system is a complex collection of nerves and specialized cells known as neurons that transmit signals between different parts of the body. Vertebrates — animals with backbones and spinal columns — have central and peripheral nervous systems.

The central nervous system is made up of the brain, spinal cord and retina. The peripheral nervous system consists of sensory neurons, ganglia (clusters of neurons) and nerves that connect to one another and to the central nervous system.

Credit: iDesign, Shutterstock

Description of the nervous system

The nervous system is essentially the body’s electrical wiring. It is composed of nerves, which are cylindrical bundles of fibers that start at the brain and central cord and branch out to every other part of the body.

Neurons send signals to other cells through thin fibers called axons, which cause chemicals known as neurotransmitters to be released at junctions called synapses. A synapse gives a command to the cell and the entire communication process typically takes only a fraction of a millisecond.

Sensory neurons react to physical stimuli such as light, sound and touch and send feedback to the central nervous system about the body’s surrounding environment. Motor neurons, located in the central nervous system or in peripheral ganglia, transmit signals to activate the muscles or glands.

Glial cells, derived from the Greek word for “glue,” support the neurons and hold them in place. Glial cells also feed nutrients to neurons, destroy pathogens, remove dead neurons and act as traffic cops by directing the axons of neurons to their targets. Specific types of glial cells (oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system) generate layers of a fatty substance called myelin that wraps around axons and provides electrical insulation to enable them to rapidly and efficiently transmit signals.

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August 24th, 2012

Researchers from the Laboratory of astrocyte biology and CNS regeneration headed by Prof. Milos Pekny just published a research article in a prestigious journal Stem Cells on the molecular mechanism that controls generation of new neurons in the brain.

Astrocytes are cells that have many functions in the central nervous system, such as the control of neuronal synapses, blood flow, or the brain’s response to neurotrauma or stroke.

Reduces brain tissue damage

Prof. Pekny’s laboratory together with collaborators have earlier demonstrated that astrocytes reduce the brain tissue damage after stroke and that the integration of transplanted neural stem cells can be largely improved by modulating the activity of astrocytes.

Generation of new neurons

In their current study, the Sahlgrenska Academy researchers show how astrocytes control the generation of new neurons in the brain. An important contribution to this project came from Åbo Academy, one of Sahlgrenska’s traditional collaborative partners.

“In the brain, astrocytes control how many new neurons are formed from neural stem cells and survive to integrate into the existing neuronal networks. Astrocytes do this by secreting specific molecules but also by much less understood direct cell-cell interactions with stem cells”, says Prof. Milos Pekny.

Image shows GFAP stained cortex from a TgAPP mouse showing activated astrocytes from a different study.

Important regulator

“Astrocytes are in physical contact with neural stem cells and we have shown that they signal through the Notch pathway to stem cells to keep the birth rate of new neurons low. We have also shown that the intermediate filament system of astrocytes is an important regulator of this process. It seems that astrocyte intermediate filaments can be used as a target to increase the birthrate of new neurons.”

Target for future therapies

“We are starting to understand some of the cellular and molecular mechanisms behind the control of neurogenesis. Neurogenesis is one of the components of brain plasticity, which plays a role in the learning process as well as in the recovery after brain injury or stroke. This work helps us to understand how plasticity and regenerative response can be therapeutically promoted in the future”, says Prof. Milos Pekny.

Source: Neuroscience News

July 16th, 2012

Spinal Muscular Atrophy affects one in 6,000 children and has no known cure.

A team of University of Missouri researchers has found that introducing a missing gene into the central nervous system could help extend the lives of patients with Spinal Muscular Atrophy (SMA) – the leading genetic cause of infantile death in the world.

SMA is a rare genetic disease that is inherited by one in 6,000 children who often die young because there is no cure. Children who inherit SMA are missing a gene that produces a protein which directs nerves in the spine to give commands to muscles.

The MU team, led by Christian Lorson, professor in the Department of Veterinary Pathobiology and the Department of Molecular Microbiology and Immunology, introduced the missing gene into mice born with SMA through two different methods: intravenously and directly into the mice’s central nervous systems. While both methods were effective in extending the lives of the mice, Lorson found that introducing the missing gene directly into the central nervous system extended the lives of the mice longer.

Mice born with spinal muscular atrophy typically only live five or six days. Researchers introduced the SMN gene into the mice’s central nervous systems and were able to extend their lives 10-25 days longer. The mice in the picture have spinal muscular atrophy.

“Typically, mice born with SMA only live five or six days, but by introducing the missing SMN gene into the mice’s central nervous systems, we were able to extend their lives 10-25 days longer than SMA mice who go untreated,” said Lorson, who works in the MU Bond Life Sciences Center and the College of Veterinary Medicine. “While this system is still not perfect, what our study did show is that the direct administration of the missing gene into the central nervous system provides some degree of rescue and a profound extension of survival.”

There are several different types of SMA that appear in humans, depending on the age that symptoms begin to appear. Lorson believes that introducing the missing gene through the central nervous system is a way to potentially treat humans regardless of what SMA type they have.

“This is a treatment method that is very close to being a reality for human patients,” Lorson said. “Clinical trials of SMA treatment using gene therapy are likely to begin in next 12-18 months, barring any unforeseen problems.”

Source: Neuroscience News

ScienceDaily (May 31, 2012) — Rats with spinal cord injuries and severe paralysis are now walking (and running) thanks to researchers at EPFL. Published in the June 1, 2012 issue of Science, the results show that a severed section of the spinal cord can make a comeback when its own innate intelligence and regenerative capacity is awakened. The study, begun five years ago at the University of Zurich, points to a profound change in our understanding of the central nervous system. According to lead author Grégoire Courtine, it is yet unclear if similar rehabilitation techniques could work for humans, but the observed nerve growth hints at new methods for treating paralysis.

Test subject takes first steps up stairs after neurorehabilitation with a combination of robotic harness and electrical-chemical stimulation. (Credit: EPFL/Grégoire Courtine)

"After a couple of weeks of neurorehabilitation with a combination of a robotic harness and electrical-chemical stimulation, our rats are not only voluntarily initiating a walking gait, but they are soon sprinting, climbing up stairs and avoiding obstacles when stimulated," explains Courtine, who holds the International Paraplegic Foundation (IRP) Chair in Spinal Cord Repair at EPFL.

Waking up the spinal cord

It is well known that the brain and spinal cord can adapt and recover from moderate injury, a quality known as neuroplasticity. But until now the spinal cord expressed so little plasticity after severe injury that recovery was impossible. Courtine’s research proves that, under certain conditions, plasticity and recovery can take place in these severe cases — but only if the dormant spinal column is first woken up.

To do this, Courtine and his team injected a chemical solution of monoamine agonists into the rats. These chemicals trigger cell responses by binding to specific dopamine, adrenaline, and serotonin receptors located on the spinal neurons. This cocktail replaces neurotransmitters released by brainstem pathways in healthy subjects and acts to excite neurons and ready them to coordinate lower body movement when the time is right.

Five to 10 minutes after the injection, the scientists electrically stimulated the spinal cord with electrodes implanted in the outermost layer of the spinal canal, called the epidural space. “This localized epidural stimulation sends continuous electrical signals through nerve fibers to the chemically excited neurons that control leg movement. All that is left was to initiate that movement,” explains Rubia van den Brand, contributing author to the study.

The innate intelligence of the spinal column

In 2009, Courtine already reported on restoring movement, albeit involuntary. He discovered that a stimulated rat spinal column — physically isolated from the brain from the lesion down — developed in a surprising way: It started taking over the task of modulating leg movement, allowing previously paralyzed animals to walk over treadmills. These experiments revealed that the movement of the treadmill created sensory feedback that initiated walking — the innate intelligence of the spinal column took over, and walking essentially occurred without any input from the rat’s actual brain. This surprised the researchers and led them to believe that only a very weak signal from the brain was needed for the animals to initiate movement of their own volition.

To test this theory, Courtine replaced the treadmill with a device that vertically supported the subjects, a mechanical harness did not facilitate forward movement and only came into play when they lost balance, giving them the impression of having a healthy and working spinal column. This encouraged the rats to will themselves toward a chocolate reward on the other end of the platform. “What they deemed willpower-based training translated into a fourfold increase in nerve fibers throughout the brain and spine — a regrowth that proves the tremendous potential for neuroplasticity even after severe central nervous system injury,” says Janine Heutschi, co-author in the study.

First human rehabilitation on the horizon

Courtine calls this regrowth “new ontogeny,” a sort of duplication of an infant’s growth phase. The researchers found that the newly formed fibers bypassed the original spinal lesion and allowed signals from the brain to reach the electrochemically-awakened spine. And the signal was sufficiently strong to initiate movement over ground — without the treadmill — meaning the rats began to walk voluntarily towards the reward, entirely supporting their own weight with their hind legs.

"This is the world-cup of neurorehabilitation," exclaims Courtine. "Our rats have become athletes when just weeks before they were completely paralyzed. I am talking about 100% recuperation of voluntary movement."

In principle, the radical reaction of the rat spinal cord to treatment offers reason to believe that people with spinal cord injury will soon have some options on the horizon. Courtine is optimistic that human, phase-two trials will begin in a year or two at Balgrist University Hospital Spinal Cord Injury Centre in Zurich, Switzerland. Meanwhile, researchers at EPFL are coordinating a nine million Euro project called NeuWalk that aims at designing a fully operative spinal neuroprosthetic system, much like the one used here with rats, for implanting into humans.

Source: Science Daily