I've been looking for a suitable model of chronic neuroinflammation, that not involves a Neurodegenerative disease directly. So, I look for LPS model and TBI, wondering which model is better for evaluate chronic microglial activation.
Studying the inflammatory phenomena provoked by progressive and recurrent traumatizations of brain tissues can no doubt further our understanding of unexplained neurodegenerative diseases/cryptic neuroinflammatory conditions. Which might hardly be the case the other way round!
Greetings. TBI is certainly a very good way to study chronic neuroinflammation. However, TBI is a spectrum and you need to choose which part of the spectrum is suitable for your studies. mTBI does have inflammation but the degree of inflammation may be too mild for the sensitivity of your studies. perhaps CTE will suit your studies the best and it has tremendous practical, especially social, impact. thanks.
Wouldn't it be of interest to study the auto-immunizing effects of experimentally produced TBI lesions which can be compared to the lesions discussed in the blog project
What deals the brain such blows, synchronous (at least double) hits - in an exemplary case of multiple sclerosis?
Multiple sclerosis, MS, is viewed as a matter of ongoing random attacks on the central nervous white matter.
Neurologists diagnose a chronic persistence/recurrence of such attacks if they register central nervous dysfunctions which
(a) Can't be traced back to a disease they know,
(b) Point to an affection of at least two distant places of the patient's brain respectively spinal cord,
(c) Manifest in keeping with one of two convened on time-schedules.
How neurological examinations prove the said random attacks, their white matter-orientated mode of spread, has never been shown.
To all appearances, the practice contradicts what is shown at
http://www.msdiscovery.org/news/news_synthesis/322-more-meets-eye
The caption of the time-lapse video speaks of spots that form and grow, shrink and disappear - none causing a flaring-up of symptoms.
At a closer look, the given sequences disclose mind-boggling sights.
The grandest plaque is seen to pop up alone, backward, deep in one cerebral hemisphere, and project an uneven halo resurging in a second wave (top panels).
Two nearly as extensive plaques erupt simultaneously in the same hemisphere.
The anterolateral one splashes its halo forwards at a remarkable speed (right top panel).
The posterior one explodes a sizeable preexistent plaque.
All recede and leave no residuum.
Cone- and club-shaped, in part old, ventricle-based lesions fluctuate, flicker and ripple along the circumference of the ventricular angle - paradoxically more so in the hemisphere with the less conspicuous outer plaque eruptions.
Seen in context with the mutual displacements taking place between peripheral plaques and ventricle-based lesion cones, this gives the impression of an interplay of in part competing, in part alternating mass effects of larger lesion developments.
Ventricle-based lesions waver up in grey and white matter alike (top left panel) and flare up simultaneously in distant locations - one projecting from a frontal horn while another shines up near the other atrium (top right panel).
In the end a tell-tale, in fact, the most revealing picture emerges.
A small lesion extending along the posterior ventricular angle abruptly shoots forward and pushes out, at right angles, anteriorly a broad cone and posteriorly, arising from a scarcely perceptible stalk, a slender club.
What sheds light on the nature of the given phenomenon is its repeatedly rediscovered vein-relationship.
Recently a series of papers began focusing on the significance of the “central vein sign”, also trivialized as “central vessel sign”. It addresses the question of how far a certain percentage of brain lesions that show as their axis or center a vein might contribute to making a diagnosis of MS. https://www.ncbi.nlm.nih.gov/pubmed/?term=(central+vein+sign)+AND+(multiple+sclerosis)
It shows the importance of approaching the topic rather qualitatively than quantitatively, in reviewing all the pertinent pieces of evidence, in depth.
The local vascular anatomy leaves no doubt that the changes seen to emerge along the ventricular border (top panels) must stem from veins that join the internal cerebral veins. To be precise, from the most proximal and downstream located parts of their intraparenchymal course. This indicates the changes’ mechanical, traumatic origin.
The given lesions' countercurrent propagation, their advancing in the opposite direction to the normal venous flow direction appears no less obvious. The corresponding findings can only be accounted for by blood volumes or pressure waves surging up from major neck veins.
These facts form an impregnable argument in support of the changes’ physical and hemodynamic causation, proposed a number of years ago.
https://doi.org/10.24019/jtavr.29
There is a third, widely missed aspect of the central vein sign that appears even more relevant for raising its diagnostic impact. It highlights a further blind spot of the prevailing interpretations of multiple sclerosis.
The ways in which MS lesions burst forth from their central veins, the pathologist's parent veins, their veins of origin, seem not to have been monitored in vivo to this very day.
Observations made post-mortem, in studying serially sectioned MS brains, disclose another circumstance which appears conducive to facilitating the due appreciation of the diagnostic value of the central vein sign.
There is the depiction, of Mark Scheinker, of an MS lesion splashing out just to one side of its vein - see Fig. A at http://www.ms-info.net/evo/msmanu/1029.htm
There is further Torben Fog’s compelling demonstration and documentation of a scarcely known fact: The ways in which cerebral MS lesions spread deviates as a rule from the axis of their veins of origin (references at www.ms-info.net).
Fog’s picture of a grotesquely dilated vein stem transitioning into delicate feeding veins points anew to a primarily proximal affection of the lesions' veins. It appears corroborated and extended by the in vivo findings of acute, transient dilations of not only lesion veins but also internal cerebral veins of MS patients (Zeng C ea. Cerebral vein changes in RRMS demonstrated by 3D enhanced T2*-weighted angiography. Eur Radiol 2013; 23(3): 869-78).
The joint and coincident eruptions of both lasting lesions and fleeting concussive effects - irrespective of frequent indications of a competitive lesion-behaviour - await equally their being accounted for in physical terms.
A variety of factors comes here into play.
The slower the rise of the blood and pressure waves which burden the cerebral veins from particular neck veins, the more evenly distributed the straining of their tributary veins and of these veins’ surroundings will be. The waves producing the cerebral changes emerge in synchrony.
Retrograde venous waves will the rather be detrimentally effective inside the brain the higher the speed and height of their ascent. Neither of which has ever been focused upon or monitored.
Any kind of mechanical or biomechanical impact exerted on, in the first instance, extracranial collecting veins relating to separate veins inside the craniovertebral space thereby hinders, respectively shortens the time window available for the intracerebral venous activities under discussion.
This applies, to a minor degree, also to impacts on large arterial vessels which connect to arteries that feed brain and spinal cord and ultimately even to massive impacts on the softer parts of the spine.
What levels out the pressure gradients soaring up due to, and between competing volume inputs into the craniovertebral space are first displacements of cerebrospinal fluid. Under particularly unfavourable circumstances, such of soft nervous tissues which the intervening space contains.
Any kind of competing volume input into both cranial cavity and spinal canal so ultimately reduces, and spatially confines, the repercussions of venous blood and pressure waves surging up from large neck veins into the brain.
Course, length and flow resistance of the venous channels which direct the venous pressure rises from the neck up into the brain prime the given activities in critical ways.
What is ultimately decisive is the wide range of possible interactions of unusual biomechanical and structural factors which accounts for the abrupt surging up of venous express pressures from the neck into the brain.
A few disconnected aspects of this problem have as of yet been dealt with in the papers dedicated to the subject of chronic cerebrospinal venous insufficiency (CCSVI).
The individual dispositions to the given hemodynamic events need yet to be evaluated in their natural context. This as much from a structural as functional viewpoint.
The chapter “Revealing what’s below the tip of the MS-pathology iceberg” of the text attending our video envisages the gray-matter pathology as "the Trojan horse of multiple sclerosis [research]".
Even puzzling together all the pieces of evidence which accrued on this topic during the last hundred-and-fifty years might contribute little to a better understanding of the phenomena indicated above.
Multiple sclerosis research can yet be quite confident to find a way of escape from the intricate maze of its conceptual labyrinth in clinging to its red or Ariadne thread: the central vein sign.
It just needs to begin with beginning to detect its truly singular properties also in vivo.
Thank you for considering vein-induced TBI besides lipopolysaccarid induced TBI. Sought to render the suggestion more precise in asking:
What deals the brain such blows, synchronous (at least double) hits - in an exemplary case of multiple sclerosis?
Multiple sclerosis, MS, is viewed as a matter of ongoing random attacks on the central nervous white matter.
Neurologists diagnose a chronic persistence/recurrence of such attacks if they register central nervous dysfunctions which
(a) Can't be traced back to a disease they know,
(b) Point to an affection of at least two distant places of the patient's brain respectively spinal cord,
(c) Manifest in keeping with one of two convened on time-schedules.
How neurological examinations prove the said random attacks, their white matter-orientated mode of spread, has never been shown.
To all appearances, the practice contradicts what is shown at
http://www.msdiscovery.org/news/news_synthesis/322-more-meets-eye
The caption of the time-lapse video speaks of spots that form and grow, shrink and disappear - none causing a flaring-up of symptoms.
At a closer look, the given sequences disclose mind-boggling sights.
The grandest plaque is seen to pop up alone, backward, deep in one cerebral hemisphere, and project an uneven halo resurging in a second wave (top panels).
Two nearly as extensive plaques erupt simultaneously in the same hemisphere.
The anterolateral one splashes its halo forwards at a remarkable speed (right top panel).
The posterior one explodes a sizeable preexistent plaque.
All recede and leave no residuum.
Cone- and club-shaped, in part old, ventricle-based lesions fluctuate, flicker and ripple along the circumference of the ventricular angle - paradoxically more so in the hemisphere with the less conspicuous outer plaque eruptions.
Seen in context with the mutual displacements taking place between peripheral plaques and ventricle-based lesion cones, this gives the impression of an interplay of in part competing, in part alternating mass effects of larger lesion developments.
Ventricle-based lesions waver up in grey and white matter alike (top left panel) and flare up simultaneously in distant locations - one projecting from a frontal horn while another shines up near the other atrium (top right panel).
In the end a tell-tale, in fact, the most revealing picture emerges.
A small lesion extending along the posterior ventricular angle abruptly shoots forward and pushes out, at right angles, anteriorly a broad cone and posteriorly, arising from a scarcely perceptible stalk, a slender club.
What sheds light on the nature of the given phenomenon is its repeatedly rediscovered vein-relationship.
Recently a series of papers began focusing on the significance of the “central vein sign”, also trivialized as “central vessel sign”. It addresses the question of how far a certain percentage of brain lesions that show as their axis or center a vein might contribute to making a diagnosis of MS. https://www.ncbi.nlm.nih.gov/pubmed/?term=(central+vein+sign)+AND+(multiple+sclerosis)
It shows the importance of approaching the topic rather qualitatively than quantitatively, in reviewing all the pertinent pieces of evidence, in depth.
The local vascular anatomy leaves no doubt that the changes seen to emerge along the ventricular border (top panels) must stem from veins that join the internal cerebral veins. To be precise, from the most proximal and downstream located parts of their intraparenchymal course. This indicates the changes’ mechanical, traumatic origin.
The given lesions' countercurrent propagation, their advancing in the opposite direction to the normal venous flow direction appears no less obvious. The corresponding findings can only be accounted for by blood volumes or pressure waves surging up from major neck veins.
These facts form an impregnable argument in support of the changes’ physical and hemodynamic causation, proposed a number of years ago.
https://doi.org/10.24019/jtavr.29
There is a third, widely missed aspect of the central vein sign that appears even more relevant for raising its diagnostic impact. It highlights a further blind spot of the prevailing interpretations of multiple sclerosis.
The ways in which MS lesions burst forth from their central veins, the pathologist's parent veins, their veins of origin, seem not to have been monitored in vivo to this very day.
Observations made post-mortem, in studying serially sectioned MS brains, disclose another circumstance which appears conducive to facilitating the due appreciation of the diagnostic value of the central vein sign.
There is the depiction, of Mark Scheinker, of an MS lesion splashing out just to one side of its vein - see Fig. A at http://www.ms-info.net/evo/msmanu/1029.htm
There is further Torben Fog’s compelling demonstration and documentation of a scarcely known fact: The ways in which cerebral MS lesions spread deviates as a rule from the axis of their veins of origin (references at www.ms-info.net).
Fog’s picture of a grotesquely dilated vein stem transitioning into delicate feeding veins points anew to a primarily proximal affection of the lesions' veins. It appears corroborated and extended by the in vivo findings of acute, transient dilations of not only lesion veins but also internal cerebral veins of MS patients (Zeng C ea. Cerebral vein changes in RRMS demonstrated by 3D enhanced T2*-weighted angiography. Eur Radiol 2013; 23(3): 869-78).
The joint and coincident eruptions of both lasting lesions and fleeting concussive effects - irrespective of frequent indications of a competitive lesion-behaviour - await equally their being accounted for in physical terms.
A variety of factors comes here into play.
The slower the rise of the blood and pressure waves which burden the cerebral veins from particular neck veins, the more evenly distributed the straining of their tributary veins and of these veins’ surroundings will be. The waves producing the cerebral changes emerge in synchrony.
Retrograde venous waves will the rather be detrimentally effective inside the brain the higher the speed and height of their ascent. Neither of which has ever been focused upon or monitored.
Any kind of mechanical or biomechanical impact exerted on, in the first instance, extracranial collecting veins relating to separate veins inside the craniovertebral space thereby hinders, respectively shortens the time window available for the intracerebral venous activities under discussion.
This applies, to a minor degree, also to impacts on large arterial vessels which connect to arteries that feed brain and spinal cord and ultimately even to massive impacts on the softer parts of the spine.
What levels out the pressure gradients soaring up due to, and between competing volume inputs into the craniovertebral space are first displacements of cerebrospinal fluid. Under particularly unfavourable circumstances, such of soft nervous tissues which the intervening space contains.
Any kind of competing volume input into both cranial cavity and spinal canal so ultimately reduces, and spatially confines, the repercussions of venous blood and pressure waves surging up from large neck veins into the brain.
Course, length and flow resistance of the venous channels which direct the venous pressure rises from the neck up into the brain prime the given activities in critical ways.
What is ultimately decisive is the wide range of possible interactions of unusual biomechanical and structural factors which accounts for the abrupt surging up of venous express pressures from the neck into the brain.
A few disconnected aspects of this problem have as of yet been dealt with in the papers dedicated to the subject of chronic cerebrospinal venous insufficiency (CCSVI).
The individual dispositions to the given hemodynamic events need yet to be evaluated in their natural context. This as much from a structural as functional viewpoint.
The chapter “Revealing what’s below the tip of the MS-pathology iceberg” of the text attending our video envisages the gray-matter pathology as "the Trojan horse of multiple sclerosis [research]".
Even puzzling together all the pieces of evidence which accrued on this topic during the last hundred-and-fifty years might contribute little to a better understanding of the phenomena indicated above.
Multiple sclerosis research can yet be quite confident to find a way of escape from the intricate maze of its conceptual labyrinth in clinging to its red or Ariadne thread: the central vein sign.
It just needs to begin with beginning to detect its truly singular properties also in vivo.
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