 nerve injury can be of various severity and can occur due to a multitude of causes now the causes can be suppose if there is a pull of nerves then they can be compression nerve injury where the nerve can become compressed like suppose you have slept in an odd position it can cause an injury to radial nerve it can cause wrist drop then sometimes in anesthetized people if proper care is not taken then it can cause compression of the ulnar nerve common peronial nerve so the position has to be maintained in case of anesthetized people then they can be cut injuries that can also cause nerve injuries apart from this a lot of diseases basically neuropathies in them also the changes occur as in nerve injury so they can be multiple sclerosis they can be amyotropic lateral sclerosis then leprosy so in all these diseases also we will get the pathological changes same as we get in trauma injuries okay so now let's see that how the severity of nerve injuries is classified and what are the changes which can occur in case of nerve injury so for that first we should know a little bit about the structure of a nerve now remember that when we are talking of a nerve we are not talking of a single neuron nerve is basically a collection of a lot of neurons so here this is showing a cross section of a nerve and you see that this outer black lining it is basically a connective tissue covering which is surrounding a lot of bundles of neurons so this outermost connective tissue covering is known as epineurium then inside you see that there are a lot of bundles this blue colour it is showing the bundles of lot of neurons so this is also a covering this covering is known as perineurium so the bundle of neurons which is surrounded by perineurium basically forms a fascicle then each neuron also you see it is surrounded by a connective tissue covering so to understand it we'll just try to pull out a fascicle and this is one single neuron which has been pulled out and it's a myelinated neuron this is the myelin sheath so this gray coloured it is also a connective tissue covering surrounding the myelinated neuron in this case and this covering is known as endoneurium so outermost covering the up covering is epineurium the innermost in covering is the endoneurium and the one which is surrounding a number of nerve fibres that is the perineurium which forms a fascicle so the severity of a nerve injury is classified depending on how much of this structure is affected basically there are two classifications of nerve injury one is the sedans classification a simpler classification which says that the first level of nerve injury is neuropraxia in neuropraxia what happens so that the entire nervous structure is intact and it is only a functional loss which is occurring basically in this case there is demyelination of the neuron and this will affect the conduction of the nerve impulse but you see anatomically the structure everything will be intact second level of nerve injury severity is axonatomesis in axonatomesis there is injury to the nerve fibre however all the connective tissue sheets that is the endoneurium the perineurium and the epineurium all are intact but there is some discontinuity in the axon right so discontinuity in the axon but overall all the connective tissue sheets intact is known as axonatomesis third level is neuratomesis neuratomesis is when the connective tissue sheets are also disrupted along with the discontinuity of the axon so in neuratomesis there can be discontinuity of endoneurium only and the perineurium and epineurium may be intact there may be discontinuity of endoneurium plus perineurium and third one they can be that to all the three that is endoneurium perineurium and epineurium all are disrupted so that is the sedans classification neuropraxia basically functional loss then axonatomesis then third is neuratomesis now in this you see neuratomesis actually the detail that which connective tissue sheet is injured is not mentioned why this is important because ultimately it affects whether the regeneration of the neuron will take place or not so to elaborate that there is another classification which came little later than sedans classification that is known as cinderlands classification in this classification there are five degrees and first degree is basically same as that of the neuropraxia that is there will be functional loss then second degree is same as axonatomesis that is there there will be axonal discontinuity with all the sheets intact now third is where there is axonatomesis plus there is injury to the endoneurium as well in the fourth there is endoneurium plus perineurium injury while in the final one all the sheets that is endoneurium perineurium and epineurium everything is disrupted basically classically you see sedans classification talks about disruption of the connective tissue sheet mainly the outer one that is the epineurium it doesn't detail so here these third and fourth degrees do not have a counterpart in sedans classification that's all so it's a more detailed classification okay so now what so there will be certain changes which occur in the neuron after the injury so what are these changes basically whenever an injury occurs there is influx of calcium in the neuron and this leads to activation of certain enzymes that is a calcium dependent proteases and calcium dependent lipases so owing to this a number of events start happening in the neuron so first is that as soon as there is injury there is functional loss that is the transmission of the nerve impulse will be affected that is the first immediate thing which you will see and later on this will be followed by the physical degeneration so suppose this is the site of injury where this part is showing the cell body of the neuron and this part is the axon so if this is the site of the injury you see the neuron has been cut into two fragments there is axonal discontinuity so if this is the site of injury basically the neuron has been divided into a distal segment to the injury and a proximal segment to the injury so there will be two types of changes changes which are distal to injury and changes which occur proximal to injury now the changes which occur distal to injury were described by august waller in 1850 and that's why it is known as valerian degeneration also because it is distal it is also known as ortho-grade degeneration so what are these changes which occurring in the part of the neuron that is distal to the injury so first is there is cytoskeletal network degeneration see within the neuron there are lot of cytoskeletal elements they are basically acting as tracks for carrying the material from the cell body to the axon terminal so there is cytoskeletal network degeneration plus this myelin and the cell membrane also disintegrate the breakdown so something like this then what happens you know that this myelin is basically formed by the schoen cell membrane isn't it so schoen cell release certain chemo attractants which cause recruitment of phagocytic cells so lot of phagocytic cells that is macrophages come and invade the area of the injury in the distal segment so this green color is showing the macrophages and you know that macrophages are basically the debris cleaner so they will start eating all the debris which is generated due to the disintegration of myelin the breakdown of the membrane and the cytoskeletal network yeah by the way these calcium dependent lipases which I told they cause they are the ones which cause the membrane breakdown and myelin degeneration okay so yeah we were talking about the recruitment of the phagocytic cells and the cleaning of the debris by these cells now once these macrophages come to the site they obviously clear the debris but along with that they release a cytokine that is interleukin one which causes schoen cell proliferation so here in the distal segment the proliferation of the schoen cell will start which is known as glyosis so see schoen cell are the ones which release chemo attracting to cause the recruitment of phagocytic cells and phagocytic cells now are acting on the schoen cell causing their proliferation so finally what happens basically you see the distal segment has degenerated the membrane is not there the debris has been clean myelin has degenerated but the schoen cells are proliferated so in the distal segment we get something known as distal stump or a schoen cell columns so these schoen cell columns act like tracks it's like a road path which is provided such that if this portion wants to grow it can grow inside this already laid path by the schoen cells okay so what is the timeline of these changes I told you that functional loss is immediate then this cytoskeletal degeneration myelin and membrane loss occurs over a period of two to three days then there is a recruitment of the phagocytic cells and this schoen cell proliferation or the formation of the columns it takes around one week now what are the changes which occur proximal to the injury that is the distal segment see in the cell body that is the soma chromatolysis starts chromatolysis basically is a condition in which this cell body swells and the nucleus moves to a eccentric position it basically corners itself and rough endoplasmic reticulum there is some breakdown plus there is also degeneration here so the first node of Ranvier near to the injury till there there is a degeneration in the axon as well so these are the changes which occur proximal to injury okay but along with this the degeneration happening in the distal segment and the changes occurring in the proximal segment what happens that along with this some changes occur which promote regeneration and these changes are basically change in pattern of genes which are expressed plus there is increase in the protein and RNA synthesis in the proximal segment and the schoen cells they secrete nerve growth factor so these are the regenerative changes occurring because of this what happens this part of the axon starts giving regenerative sprouts so lot of sprouts start coming from this segment of the neuron now this it can go here here here so multiple ways these sprouts can grow but it is the schoen cells which actually guide these sprouts to the track so there are certain chemicals released from the schoen cells which act on these nerve terminals causing the nerve terminals along the path to grow now one thing you remember is that these regenerative changes occur very well in peripheral nervous system but regeneration of the neuron does not occur in central nervous system this is because in peripheral nervous system schoen cells are there which release certain growth factors and they guide the sprouts towards the path but in central nervous system it is other way around the oligodendrocytes which are surrounding the neuron they actually inhibit the regeneration they secrete certain inhibitory factors such that these sprouts do not perform and they do not grow any further is it good or bad well it appears bad but one thing you should remember that central nervous system and all the neurons are packed isn't it so you cannot allow any chance of misguidance so suppose if axonal sprouts grow and they grow some in wrong direction what will happen there is no space there isn't it so they it may go and may contact with other connections and it will create a havoc in central nervous system so physiologically it might be good but when we see this in patients it where it is very heartbreaking since the neurons in central nervous system cannot regenerate anyways there is a lot of research going on and how to promote this regenerative changes in central nervous system okay let's come back to our topic we were talking about the axonal sprouts so now once these axonal sprouts grow they can be two outcomes one that they grow back to the original target along the laid path or second these axons become entangled so here all the sprouts will get entangled to each other and they will not grow any further now this depends how severe the injury is which we discussed in the beginning so actually this neuropraxia which we said that there is no axonal discontinuity that is the grade one this has a very good prognosis no need to grow back and nothing that kind of things are not happening so it's a it has a very good prognosis axonitimesis also it has a good prognosis because the connective tissue sheets are not injured the paths are laid down so there are very less chances because the sheets are intact isn't it so there are very less chances that they will grow in different different directions on the other hand neurotimuses if the outer covering is injured or even for that matter these coverings if they are injured in that case it becomes little difficult for regeneration so in this case basically surgery helps where you suture the various connective tissue sheets together and the guidance will be done by our physiological processes by our shown self themselves okay so that was about the prognosis that how you tell about the prognosis of the nerve injury but there are certain consequences which happen one is that if the neuron doesn't regenerate what happens the area which it is supplying okay like suppose here I am showing a neuromuscular junction so what happens this is a target organ it has a receptors for the neurotransmitter which will be released now when there is degeneration these receptors increase in number we call it upregulation so there is upregulation of the receptors such that even minute release of the neurotransmitters now will excite the target organ more so that is known as denervation hypersensitivity it is a common phenomena in body whenever the concentration of the chemical goes up the receptors go down on the other hand when the chemical goes down the receptor goes up so it is a regulatory mechanism in body which in this case becomes pathological causes denervation hypersensitivity second consequence can be that there can be chain of events which can lead to nerve degeneration so suppose this is the neuron which is injured what will happen that the signal will not go to next neuron if the signal doesn't go to next neuron this neuron will also degenerate because there are certain trophic factors also so this neuron will also degenerate so that is known as antograde neuronal degeneration then the neurons which are making connections here on the cell body of the injured neuron they also get removed and what happens that this area gets occupied by glial cells so this is known as synaptic stripping so this is a phenomena which can occur and what happens that if there is an injury in one part of the brain suppose it can lead to loss of function due to some neurons in other part of the brain because the neurons may be interconnected and they all will undergo degeneration due to the chain of events which is occurring so yeah so that can also occur antograde neuronal degeneration and retrograde neuronal degeneration fine finally there can be wrong connection so even if the growth is occurring they can be formation of wrong connection so you might have heard about crocodile tear syndrome in this what happens this is a phenomena which occurs in patients of Bell's palsy where there is a palsy of seventh cranial nerve so during regeneration they can be cross connections with other nerves so what happens that there is lacrimation that is the tears which fall while eating so because they are false tears the person is not actually crying but while eating there is a stimulation of the nerve and it causes the tears to come out so that is known as crocodile tear syndrome then they can be formation of neuroma that is the entangled mass of the neuron so as I told you that there is formation of the sprouts if it doesn't grow into the path laid down by the schwann cell the schwann cell column then it gets entangled and it is very painful in case of sensory fibers well that is all about the nerve injury the classification the changes which can occur the consequences and what is the prognosis of different types of nerve injury well thanks for watching the video if you liked it do press the like button share the video with others and don't forget to subscribe to the channel physiology open thank you