Can we create neurons from another cell type? Yes!. The red-colored cells you see in the above image are neurons that were originally mice glial cells. NIH researchers have converted those into neurons using gene therapy.
Furthermore, these new neurons, they have demonstrated, can do the lost neurons’ job!.
You can read more about this amazing story on the NIH Director’s blog.
We know about neurons; do we know enough about Glial cells?
In fact, glial cells outnumber neurons. And, they are very close allies of neurons. If they do not exist, neurons cannot exist.
Types of glial cells
There are three types of glial cells: Astrocytes, Microglia, and Oligodentrocytes. The diagram below illustrates them.
As you can see, they look like stars and in contact with both neurons and the cells of the supply routes’ walls; in this case, the smallest branches of it – the capillaries. They also provide structural support to synapses. They play a crucial role in a stroke; strangely both hero and villain roles. Their members who reside as neighbors to the attacked area quickly undergo both structural and functional changes; they proliferate and form a fence. This separates the dead from the living, very much similar to the “crime scene” tapes.
This group scavenges dead cells and attack pathogens (disease-causing microbes). Their job is to maintain a healthy environment in the brain.
This group produces myelin that sheaths around axons of neurons. The myelin sheaths act as insulators that help send electrical current-based information faster.
Now, it is obvious that if they do not their job, there is no point in having neurons.
This is a special group. They act as scaffolds for baby neurons and guide them to migrate to their final destinations.
This post discusses how stroke takes away bladder control.
How do we normally control our bladder?
First, let us look at the anatomy of the structures that produce and store urine. Urine is a waste product that is filtered and passed out of the kidneys to the store-room (bladder) via two tubes (ureters).
Figure 1 below shows the tubes (ureters) that transport out urine from our kidneys and the inside view of our storage facility (bladder). As you can appreciate that the storage facility’s wall is thick. It is made up of a strong muscle called “detrusor” and stretchable to accommodate about 450-500 ml of urine.
When our bladder fills up to this much of urine, we get to know it. How?
We will receive messages continuously until we decide to empty the bladder through a web of nerve endings that cover the whole outer layer of the bladder wall. These nerve endings relay their situation to the nearest transit center which is stationed at a place of the lower part of the spinal cord. This center again relays this message to the master control center placed at the brain and awaits a signal of approval to open the gates.
Go through Figure 1 again; find out the two control gates. We have two gates: the inner gate (named inner urethral sphincter) and the outer gate (named outer urethral sphincter). These are situated in the tapering lower part of the storage facility (bladder). No sooner the transit center at the spinal cord receives the approval from the brain center, it sends to messages to the gates to open and the bladder wall to contract.
What happens in a stroke?
A stroke can attack the brain’s regulatory center and as a result, may lose the ability to control the transit center. Therefore, as soon as the bladder is getting filled, urine may go through the gates.
This does not happen among all those who face a stroke, but only among those whose a large part of the brain is attacked.
However, brain damage is not the only reason for the incontinence after stroke; it can happen due to a myriad of other factors: inability to communicate to the caregiver for assistance; delay in reaching the disposing container; delay in transferring to the commode, and some medications such as urine pill (diuretics).
Would you like to add more to this post? You can. Add your inputs into the comments section.
Carl Wernicke: image source: Wikimedia
What is Wernicke’s aphasia?
In 1874 – after Paul Broca’s discovery of Broca’s area and Broca’s aphasia – Carl Wernicke described a different type of aphasia: a type which allows talk fluently but meaningless words and sentences. In contrast to those affected with Broca’s aphasia, in which they can talk fewer than four words at a time, those affected by this type talk fluently. However, anyone can notice their problem – their words contain no meanings. And, they repeat the same word over and over again. According to Argye E. Hillis, they seem to unaware of their errors in contrast to those with Broca’s aphasia. One tends to think they are talking another language we cannot understand. Not only talking, but writing and reading also follow a similar pattern. Hence, this type of aphasia is called fluent aphasia (Broca’s aphasia is called non-fluent aphasia). Since Carl Wernicke described this, it is also called Wernicke’s aphasia.
You can find out how an individual with Wernicke’s aphasia converse with others by watching this video clip.
So, Wernicke’s aphasia occurs as a result of damage to the Wernicke’s area. Where is it in the brain?
Wernicke’s area lies in the temporal lobe (visit the journeys to the brain:2- A walk over the brain surface) at a place close to the area (auditory) that contains cells specialized in processing hearing information (Figure 1). Whenever we hear something, the hearing area receives information from the ear and then send this information to the Wernicke’s area. Similarly, whenever we see or read something, the visual area receives it and then sends that information to the Wernicke’s area. Neurons in this area work hard to retrieve suitable nouns appropriate to the context from the storeroom, set the language structure, and shoot the processed information to the Broca’s area.
How do Wernicke’s neurons connect with Broca’s neurons?
As shown in Figure 2, Wernicke’s neurons connect with Broca’s neurons through a super-highway, called “arcuate Fasciculus”. This is a bundle of neurons dedicated to this task.
How do Wernicke’s neurons die?
Wernicke’s neurons die due to disruption of the blood supply to the temporal lobe where Wernicke’s area resides. Most commonly, a blood clot which blocks a branch (the inferior branch) of the left middle cerebral artery is the culprit. This is a medical emergency – stroke. If we do not intervene more preferably within the first hour of the last known normal, the damage may become permanent because neurons die at a rate of 32,000 per second.
In aphasia, we either lose or impair the ability either to understand the language or talk – or else both depending on the extent of the brain damage. The nature of the loss or impairment varies with the area of the damage in the brain. Broca’s aphasia – a special type of aphasia occurs when the neurons die populated in the Broca’s area. You can find about the Broca’s area in my Broca area: Journeys to the brain-10
How Broca’s aphasia occurs in a stroke
Stroke – more commonly due to a blood clot – disrupts the blood supply to the brain in a speed of light; the clot plugs the anterior branch of the middle cerebral artery cutting off blood supply to the Broca’s area. Due to the lack of oxygen, neurons residing in the region begin to die en masse like trees engulfed in a massive wildfire – 32,000 neurons per second! This emergency situation, like a blow to the head, results in Broca’s aphasia.
What really happens in Broca’s aphasia?
Remember Paul Broca’s first patient? – Mr Leborgne who was named as “Monsieur tan”?. He was able to say only one word – “tan”. As in the case of “monsieur tan”, those with Broca’s aphasia do not lose speech completely; they cannot talk now as they used; because, the neurons who did the job is no more there.
Let us find out what those with Broca’s aphasia can and cannot – or difficult – to do. These problems become more pronounced when the block happens in
What those with Broca’s aphasia can do
- They can hear.
- They can read.
- They can understand simple – not complex – instructions.
What they cannot (or difficult) to do
- They can talk but only less than 4 – 5 words at a time
- They can talk simulating telegraphic speech.
- Their sentences lack grammatical sense – both in talking and writing.
- They use nouns without verbs.
- They have difficulty in repeating.
- They have a difficulty to respond to complex instructions: for example, touch nose after touching toes.
A person with Broca’s aphasia
Following video clip will help to appreciate what a person with Broca’s aphasia can and cannot do.
What is the usefulness of knowing these things?
- What they can or cannot do within a few days after the stroke help predicting the area/s of the brain affected, where neurons are dying as highlighted in the paper authored by Elisa Oschfeld et al.
- The brains of many with Broca’s aphasia do not allow them to live with those problems long; recovery can be immediate due to the restoration of blood flow as shown by Cameron Davis and their research team or may happen later possibly due to the execution of the brains’ plan B – reorganizing adjacent neurons to take over the dead neurons’ job as speculated in the paper authored by Elisa Oschfeld et al..
Broca’s area plays a very important role in our speech.
Prior to 1861, scientists debated whether the whole brain acted either as a single entity or it contains specific regions assigned to specific tasks. Pierre Paul Broca ended this debate in 1861.
One day, prior to 1861, Pierre Paul Broca examined an adult male – named Leborgne – who came with a right-sided paralysis.
Pierre Paul Broca was a surgeon who had a special interest in physical anthropology. He had been studying the association between skull shapes and sizes with evolution.
In addition to the Leborgne’s – Broca’s patient – right-sided paralysis, he was suffering from another problem: He produced only one sound with one syllable – “tan”, twice in succession, albeit fine with understanding. Since then, the hospital staff identified him as “Monsieur tan”. Paul suspected Leborgne’s problem was due to some sort of damage to the brain’s left side although there was no way to confirm it at that time. After his death, Paul dissected his brain and discovered a damaged region in Leborgne’s brain’s lower part of the left Frontal lobe.
In 1861, Paul Broca presented his findings – “our brain owns a specific area in charge of speech production” – to the world.
Three years later, Broca described 25 similar cases; all but one had a damaged area at the same place in the brain: lower part of the left Frontal lobe – just above the left eye’s orbit.
With that, he ended the great debate at that time: “the brain owns specialized areas for specific functions”.
However, now, we know that this is not 100% accurate.
Since then, the medical community has continued to name this area in the left hemisphere as the “Broca’s area” to recognize his exemplary work. And, the inability to produce speech as a result of damage to this area is named as “Broca’s Aphasia”.
Brodmann 44 and 45
Much later, in 1909, another expert – Brodmann – identified two parts of Broca’s area; these parts were named Brodmann 44 and 45 which are depicted in the following sketch.
The most recent research has shown that the Brodmann 45 is more active in meaningful language processing together with the area 44. Moreover, it also has shown that its surrounding areas become active in more general domain-specific cognitive functions.
The Broca’s area rests on the lower part of the left Frontal lobe. I invite you to re-visit the Journeys to the brain: 2 – A walk over the brain surface which introduces different lobes of the brain. For easy reference, I have included a graphic that appeared in my earlier journey to the brain:2.
However, most recently, researchers, using sophisticated MRI technology, showed that Leborgne’s brain damage had gone beyond what we now have typically known as Broca’s area. This fact raised to doubt the exact role of Broca’s area in speech production.
Using the latest technological advancement, researchers have shown that Broca’s area mediates the interaction between the Temporal lobe which helps us to process listening and the motor area of the Frontal lobe, the area sends signals to speak.
neurons in the brain (Illustration credit: Benedict Campbell. Wellcome Images firstname.lastname@example.org: CC BY-NC-ND 2.0
Until 1887, our brain and the spinal cord was considered as composed of a continuous single network. Santiago Cajal, in 1887, using a stain developed by Camilio Golgi, showed separate cells connected through spaces. However, Camilio Golgi disputed the claim. Wilhelm von Waldeyer-Hartz named these cells as “neurons”.
Previously, we entered the neuron forest. Neurons are like trees in a forest. They are elegant, superior, and live wonderful lives. On average, our brain owns about 100 billion neurons.
What is a neuron?
A neuron is a specialized cell, only found in the brain and its connected nervous system. The following illustration describes parts of a typical neuron; however, we can find very highly specialized neurons in different parts of the brain.
Like any other cell, a neuron owns a cell body – the main control center. It contains a nucleus and other essential structures to maintain its life such as mitochondria to produce energy and other apparatus that transport substances within the fluid inside the cell.
You can find dendrites as tree-like structures that are very much closer to the cell body. These branches receive messages from other neurons and bring those messages toward the cell body. In some places such as in Cerebellum, one neuron can have even about 200,000 branches.
This is the tube-like structure that propagates received signals towards the axon terminals with the aim of transmitting to other neurons or its endpoint for action. Axons’ length can vary from millimeters to a meter. For example, axons that propagate information from the spinal cord to toes should be very lengthy. Sometimes, one axon owns many terminals. As a result, these axons can send messages to many neurons at the same time. On the other hand, some neurons such as the cells in the retina where information from eyes is processed do not have axons.
The axons that transmit information for action (motor neurons) have a thick covering, called “myelin sheaths”. They act like an insulator in a wire to send information faster.
Myelin sheaths are not parts of a neuron; these are produced by its supportive cells, called, “Glial cells”.
As you can see, these sheaths are interrupted from place to place; that is to recharge the electric signals. These places are called “nodes of Ranvier” because those were first described by Ranvier.
How neurons transmit information
The following GIF explains vividly how this happens though an axon. As you can see when the axon is at rest, the inside of the cell membrane is negatively charged; exactly – 70 millivolts than the outside. It is maintained using pump. It is costly because it pumps out three sodium ions while pumping in two potassium ions. This pump uses energy using one ATP molecule at each time.
This video clip explains the above mechanism more clearly too:
How neurons communicate each other: The synapse
Once a message reaches the axon’s terminal, it has to travel through a small pond to pass it on the next neuron. It is no more an electric transmission. Rather, it is a chemical transmission.
The following diagram drawn by Thomas (the link given above) illustrates this pond and the activities that take place when an electrical message reaches the cup-shaped terminal. The other end is the beginning of a dendrite.
The lower end which faces the axon terminal is the dendritic end. The electrical impulse stimulates chemical-filled vesicles and they release their chemicals into the cleft. Finally, the receptors of the dendrites capture those chemicals; it triggers electrical impulses in the dendrites and travels until it reaches the neurons’ axon terminals.
So, the neuron – the messenger – does not go anywhere; only the message – after translating the message’s electrical form into a chemical form – travels from one neuron to another. That is why the whole neuron system consists of about 100 billion neurons.
The following video clip explains how a synapse operates:
Different message types
Although the mechanism is the same, neurons transmit different message types; either to carry on certain tasks such as moving a hand or to recognise certain sensations such as smell, touch, pain etc. The motor neurons carry messages to carry or not to carry movements. The sensory neurons bring messages about sensations – touch, pain, hearing, seeing etc.
Our brain contains about 100 billion neurons; it looks like a neuron forest. because a neuron is more or less similar to a tree.
These are cells – a special kind of cells. At one end, it sprouts a large number of very thin short threads – “dendrites”. The ends of these receive electrical signals from other neurons via small fluid-filled ponds – “synapses”. The received signals pass along until it reaches the tree (cell) body. From there, it shoots away to the next neuron through another a thicker branch; it is named “Axon”. So, dendrites take electrical signals from previous neurons, bring those to the cell body of the neuron, and the Axon transmits those signals to the next neuron – sometimes to muscle endings and organs. We own about 100 billion neurons; So, it is, in fact, a huge “neuronal forest”.
Santiago Cajal: A Nobel Laureate
For the first time, Santiago Cajal – a Spanish medical specialist – stained neuron cells with a special stain, called gold stain. It colored only the neurons. In fact, he improved Camillo Golgi’s method. Cajal’s neuronal mapping became phenomenal which elevated him to share the prestigious Nobel prize with Camillo Golgi in 1906. At that time, people thought that the brain was an interconnected unbroken network. The Cajal Institute has been carrying his legacy since then until now in Spain through a range of academic programs dedicated to neurology.
Not only was he a medical scientist, but he was also a gifted artist. As a result, he used his artistic skill to draw various shapes of neurons. Enter into his neuron forest. now. I took the following drawings from an online teacher resource published by Weisman Art Museum for classroom activities. This excellent resource is freely available. You can access
A Pyramidal Neuron drawn by Cajal
Appreciate that how precisely he has drawn the following. This type of neurons
The Neuronal forest by Cajal
More recently, with the advancement of the technology, we can now see how our neuron forest look like in 3 dimensional view.
Enter into the neuron forest; enjoy the universe of synapases;
As soon as a stroke strikes within minutes brain cells – neurons and glial cells – begin to die; each second costs as many as 32,000 neuron cells, 230 million synapses, and 200 meters of axonal fibers. In terms of minutes, each passing minute costs 1.9 million neuron cells, 13.8 billion synapses, and 12 kilometers of axonal fibers (Saver J.L. 2005).
So, every second
“Time is Brain”, but only as a general rule
As far back as in 1993, Dr. Camilo R. Gomez coined this exhortation – “Time is Brain” – in an editorial to the Journal of Stroke and Cerebrovascular Diseases.
Wait; there is a caveat.
In 2018, Dr. Gomez updated his “Time is Brain” slogan!
That brain cells’ dying speed is not linear. It depends on the affected person’s collateral system. What does that mean? We all have a backup blood supply mechanism, just in case. When the main supply route blocks, our alternate support system gets activated. We still do not know how wide this mechanism operates. What we do know is that it’s spread varies from person to person.
In other words, while acknowledging that the “Tims is Brain” is still a valid slogan, we still proceed to act on the F.A.S.T. even the golden hour is elapsed.
The critical time of no return
How long neurons can survive without blood?
This is a very important question I had when I was writing this post. As far back as 1981, Jones and a team of researchers attempted to find an answer to this question using monkeys. They found no irreversible damage when the blood supply was restored within 30 minutes (Jones et al. 1981).
There was another interesting finding.
When the blood supply was not completely blocked out – only reduced to 12 – 18ml/100g/min (mild-moderate ischemia) – even after 2 – 3 hours, the affected cells survived! That means only when the blood supply reduced to less than 10-12ml/100g/min, the damage became irreversible (Jones et al. 1981).
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Within the first 3 – 8 days after a stroke, the affected area swells more than the volume of this area. Then, re-organisation and retraction remove the dead tissues resulting in a volume smaller than the pre-affected brain area within the next 2 weeks to 3 months time (Saver J.L. 2005).
Brain’s internal collateral systems: (Image source: Stroke Journal)
You must have read my post on Brain’s blood flow: Journeys to the brain- 4. It is not the only oxygen and food supply route to the brain; we have our brain’s alternate collateral supply system too – just in case. This brain’s collaterals are a very recent finding. However, we have been known about the primary source of these collaterals: the Circle of Willis.
Circle of Willis
The yellow-colored circle is the “Circle of Willis” (Figure 1). It is well connected to the red-colored main supply routes.
In addition to the Circle of Willis, we own a secondary mechanism too. In other words, our brain has an alternate mechanism to keep brain cells alive whenever its blood supply is interrupted. Figure s summarises that channel system. David Liebeskind published an article about this system in the Stroke journal in 2003. According to him, these collaterals divert blood into affected regions. I have cited the url link below for those who are interested in reading about this topic more.
These collaterals, as we can easily understand, should be vital to minimizing the damage that may cause by an ischemic stroke. The author says that the extent of these collateral systems determines the clinical outcome.
The collaterals keep the neurons and their supportive cells alive until a rescue operation from us arrives. Hence, the extent of collaterals at the “war zone” is vital according to Jung Simon et al. (2017).
Jung S, Wiest R, Gralla J, McKinley R, Mattle H, Liebeskind D. Relevance of the cerebral collateral circulation in ischaemic stroke: time is brain, but collaterals set the pace. Swiss Med Wkly. 2017;147:w14538. Published 2017 Dec 11. doi:10.4414/smw.2017.14538
The term, “stroke” refers to a sudden stoppage of blood flow to a part of the brain. It can happen either due to a block to a supply route (artery) or a blast (rupture) in a supply route.
The block to a supply route occurs due to a blood clot that lodges within a blood supplying vessel, an artery, or one of its smaller branches.
- In the medical field, “stroke” is called “cerebrovascular accident” (in short, CVA).
- A stroke due to blockage due to a blood clot is called “ischemic stroke”.
- A stroke due to a broken supply route is called “hemorrhagic stroke”.
From the two types, the “ischaemic strokes” are much commoner than the “hemorrhagic strokes”. In the US, as much as 80 percent strokes are ischemic strokes according to the US government website.
There are common places where ischemic stroke strikes. One place is the junction where the main supply route (common carotid artery) divides into two smaller branches: internal and external. (Read the blood flow: Journeys to the brain-4.). These clots usually travel higher up and block a smaller artery. The extent of the damage depends on the size of the clot and part of the brain it blocks. See Figure 1.
Sometimes, a clot can originate within the heart itself too.
In a hemorrhagic stroke, blood seeps through from an arterial branch either due to a leak
Transient Ischaemic attack (TIA): “mini-stroke”
This term is used as its name implies a very brief attack due to a temporary blockage of a blood vessel. The block is caused by a very small blood clot which will dislodge by itself. This is considered a warning. However, it is a medical emergency meaning that we need to call 911 immediately.
The “mini-stroke” typically resolve within 24 hours; however, it can become a full-blown stroke if not attended.