Fluids and Barriers of the CNS - Latest Comments

Belorussian translation

Hazel C. Jones — 2011-08-18T14:51:54Z

This article has been translated into Belorussian by Nadejda Dobkina with permission of the authors. It can be viewed at
http://onlinepharmacycheck.com/~doc/fluidsbarrierscns-content-be

Fluid dynamics and Alzheimer's disease

Rovshan Ismailov — 2010-11-03T17:58:39Z

The current research on Alzheimer’s disease is primarily focused on the discovery of specific protein subunits as well as identification of genetic mechanisms involved in this disease. With the appearance of the “hypoperfusion” theory as well as findings from numerous population-based studies linking Alzheimer’s disease to “vascular” disorders (i.e. hypertension, atherosclerosis etc.)[1,2], it became evident that the important task for understanding Alzheimer’s disease is to thoroughly examine local fluid (i.e. cerebrospinal) dynamics. Such approach may also result in finding of successful treatments of Alzheimer’s disease.

One of the mechanisms that can describe, for instance, an association between cardiac pathology (i.e. cardiac arrhythmia) and Alzheimer’s disease is the disturbances in the dynamics of regional brain extravascular extracellular fluid[3]. Such consideration of regional brain extravascular extracellular fluid dynamics is also particularly important in light of the fact that certain waste products such as glutamate or calcium can accumulate there causing degradation of certain cellular components thus playing an important role in the pathogenesis of Alzheimer’s disease[4,5].

Such mechanism proposes that the regional brain extravascular extracellular fluid gets moved due to the cyclic changes in the vessel wall deformation, a sort of a “deformation pump”[3]. The operating principle of the “deformation pump” is in the cyclic creation of the boundary layer and in its separation. Thus the movement of the regional brain extravascular extracellular fluid happens as a result of the appearance and separation of the boundary layer at the close proximity to the vascular wall. The obvious implication of this mechanism is the primary involvement of cardiovascular system in the development of Alzheimer’s disease.

Rovshan M Ismailov, M.D., M.P.H., Ph.D.

References

[1] de la Torre JC. Impaired brain microcirculation may trigger Alzheimer's disease. Neurosci Biobehav Rev 1994; 18(3):397-401.
[2] de la Torre JC. Cerebral hypoperfusion, capillary degeneration, and development of Alzheimer disease. Alzheimer Dis Assoc Disord 2000; 14 Suppl 1:S72-81.
[3] Ismailov RM. New insights into the mechanism of Alzheimer's disease: A multidisciplinary approach . edn. Amazon Kindle, 2010.
[4] Mattson MP. Calcium as sculptor and destroyer of neural circuitry. Exp Gerontol 1992; 27(1):29-49.
[5] Khachaturian ZS. The role of calcium regulation in brain aging: reexamination of a hypothesis. Aging (Milano) 1989; 1(1):17-34.

Minocycline in Hydrocephalus

Md.Gulam Mostafa — 2010-05-31T09:59:36Z

Microglia, a migratory phagocytes remain quiescent in normal brain to provide trophic factors and improve neuronal plasticity. Conditions like ischemia, haemorrhage, hydrocephalus, brain tumor or other CNS trauma might activate neuro-inflammation and consequences are reactive gliosis. A possible therapeutic role of Minocycline, as neuroprotective, anti-inflammatory, neurodegenerative disorders like multiple sclerosis, Amytrophic lateral sclerosis, Huntington’s disease, Parkinson’s disease and in Rheumatoid arthritis have been examining elsewhere. Azithromycin, a newer macrolide of this group has high concentration in phagocytes, azithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of azithromycin are released. The concentration of azithromycin in the tissues can be over 50 times higher than in plasma. This is due to ion trapping and the high lipid solubility.

The current article is promising and oustanding shwoing the efficacy of minocycline in hydrocephalus. Azithromycin may be a better choice might require investigation, it is a stumulus to investigators to explore the therapeutic dimension of ordinary antibiotics in extraordinary fields.

Dr.Md.Gulam Mostafa, MBBS, Ph.D.
Postdoctoral Fellowship (USA)
Uttra Adhunik Medical, Dhaka, Bangladesh
e-mail: md_gulammostafa@yahoo.com

querry

Helen Williams — 2010-05-31T09:58:10Z

Lymphatics drain the human central nervous system. It is likely that this is a desirable feature of brain anatomy because of the vulnerability of the CNS caused by a need for vision, smell and hearing. The lymphatic system recruits help from the cellular immune system, which comprises B and T cells, by delivering infected lymph fluid into the blood. Brain sensation risks infection of the brain. The more we smell, see and hear, the greater our risk. High CNS pressure could encourage lymphatic flow by pushing liquid into the nose or periorbital tissue, or if higher, press on delicate lymphatic vessels and occlude them. This means that brain lymphatic flow and CNS pressure will have an unpredictable relationship. That high pressure occurs with occlusion of vessels does not mean that vessel occlusion causes raised pressure. I believe that lymphatic occlusion in the presence of high pressure can be compensated by the autonomic nervous system, so that volume regulation may briefly be more important than lymphatic flow. In the most fortunate cases, lymphatic flow alerts the immune system and autonomic brain regulation and the other body organs maintain CNS equilibrium. This happens with a bad attack of sinusitis. For others the body is overwhelmed, blood pressure cannot be maintained, the spleen is too old or too immature to respond and the brain swells briefly and then dies. This occurs with meningococcal pharyngitis. My assertion is that brain volume regulation is at least as important as the lymphatics, they depend upon each other, but that the lymphatics are in essence subservient.

Spontaneous or Iatrogenic Intracranial Hypotension?

Md.Gulam Mostafa — 2009-06-29T10:38:18Z

The authors did an excellent tedious and arrogantly expensive study without any destination. This study is just extrapolation of authors work to the existing fact in a bizarre way. Good news is a stimulus to recapitulate intracranial hypotension- SPONTANEOUS or IATROGENIC ?
Spontaneous intracranial hypotension (spontaneous CSF leaking) often difficult to diagnose and treat rather than traumatic or iatrogenic CSF leaking. RI cisternography is used but not conclusive, 30% of spontaneous CSF leaking remain undiagnosed even with RI cisternography. Early bladder filling was observed before too, nothing hypothesize or discussed about the possibility of EBF. How about the tracer concentration around the micturition center in brain ? Lumbar puncture is routinely practiced procedures in the clinical wards and PLH is a common phenomenon, not a challenge for physician. What is the suggestions for the size of needle for LP ? if it is the iatrogenic intracranial hypotension ? Nothing indicating about the spontaneous CSF leaking, totally ignored the challenging condition ?

Dr.Md.Gulam Mostafa
Department of Anatomy, UAMC
Dhaka, Bangladesh
e-mail: md_gulammostafa@yahoo.com

Correction of Authors' Error

Pippa Oakeshott — 2005-02-27T15:36:36Z

We mistakenly referred to the 2001 Casey Holter Essay "Humanity lost: the cost of cortical maldevelopment" as reference 7. It is an interesting article, but not relevant to this paragraph of our paper. We apologise for this authors' error.

Pippa Oakeshott and Gillian M Hunt

Scaling issues

Samuel Neff — 2005-02-17T16:47:59Z

This article confirms a popular explanation for the clinical observation that children with acute hydrocephalus (usually due to malfunction of an implanted CSF shunt) often have "swollen" eyes noted by their parents. I hope the authors are successful in additional human studies, so we can understand the range of variation in these channels.

An important clinical issue is the effect of brain size and size ratios on the application of these results. Many small mammals have brains that are comparable to (or within an order of magnitude of) the size of their eyes. Similarly, many large mammals have brains that are comparable in size to their peripheral olfactory systems. In humans, conversely, the brain is 1-2 orders of magnitude larger than either of these organs. So, the importance of these pathways in humans may be relatively small, not because they do not exist, but because there is so much more (CSF-producing) brain proportionately present.

Microfil marker in SAS

Martin Lubow — 2005-02-07T20:55:24Z

Important work. Well done.

Did the subarachnoid Microfil appear in arachnoid granulations and/or in dural wall tissues of cavernous sinus?