Journal of Neuroinflammation - Latest Comments

Celastrol is not an epoxide

Daniel Paris — 2013-03-21T16:24:36Z

Celastrol is present in a vine which is widely distributed in eastern and southern China (Tripterygium wilfordii) which is also known in the Chinese language as "Lei Gong Teng" (Thunder God Vine) and has a long history of therapeutic use in traditional Chinese medicine [The Editorial Board of Chinese Materia Medica of State Administration of Traditional Chinese medicine of P. R. China. Chinese Materia Medica; Shanghai Scientific and Technical Publishers: Shanghai, China, 1999; Volume 5, pp. 206:215]. Triptolide and celastrol are known active ingredients of Tripterygium wilfordii. We wrongfully referred celastrol as being an epoxide in the results section of our manuscript. Celastrol is a pentacyclic triterpenoid whereas triptolide is a diterpenoid epoxide.

EJN Blog Interview

Dimitrije Krstic — 2013-03-19T16:59:30Z

Dear Colleagues,
for those interested to hear more about a neuroinflammation model of AD pathogenesis that was inspired by the data presented in this paper and has been recently published by Nature Reviews Neurology (hypothesis) here is the link to EJN Blog Interview with Irene and me: interview. Any feedback, comments, and/or criticism are highly appreciated!!!

Fetal asphyctic preconditioning - an alternative explanation

Floris Groenendaal — 2013-02-04T15:51:06Z

Utrecht, February 4, 2013

Dear Sir,

With great interest we have read the paper of Vlassaks et al. on neuroprotection by fetal asphyctic preconditioning.

The authors conclude that fetal asphyctic preconditioning is neuroprotective through a protective inflammatory phenotype in the brain. However, both IL-6 and IL-10 were elevated in fetuses with asphyctic preconditioning just before perinatal asphyxia, so this presumed protective phenotype is not obvious at first sight.

The authors state that IL-10 is an anti-inflammatory cytokine. Perinatal asphyxia (without fetal preconditioning) results in IL-10 elevations at 2h and 6h. After fetal preconditioning and perinatal asphyxia, however, IL-10 is decreased compared to perinatal asphyxia without preconditioning. This is in contrast with the suggestion, that IL-10 is associated with neuroprotection after preconditioning. In similar way, it is not clear whether the authors think that IL-6 expression after perinatal asphyxia and reduction of IL-6 after fetal preconditioning and perinatal asphyxia is contributing to neuroprotection.
Furthermore, the authors suggest that the post-ischemic inflammatory neuronal damage is amplified by activation of the STAT signaling pathway and that inhibition of P-STAT is associated with neuroprotection. P-STAT levels are decreased after perinatal asphyxia, but are elevated after fetal preconditioning and perinatal asphyxia at 12h which is in contrast with the previous statement.

We think that there is a better explanation for their observations.
In the discussion of their paper the authors mention briefly, that fetuses subjected to fetal asphyctic preconditioning have a higher survival chance after perinatal asphyxia. Unfortunately, they do not provide data on the mortality during or after perinatal asphyxia in their model with or without preconditioning.
It is very likely that this improved survival is a result of cardiac alterations after fetal preconditioning, since death during or immediately after perinatal asphyxia is due to cardiac failure.
Cardiac functioning has not been measured in the experiments of Vlassaks et al., but preserved cardiac output during perinatal asphyxia will definitely have been a key player in the neuroprotection which was observed.

By focusing on the brain as the target organ of fetal preconditioning, the authors may have missed the importance of cerebral perfusion in neuronal damage and neuroprotection. Since this may have serious implications for future experimental and clinical neuroprotective strategies, we regret that this aspect has not been discussed in the present manuscript.

Floris Groenendaal
Cora Nijboer
Frank van Bel

Reference

Vlassaks E, Strackx E, Vles JS, Nikiforou M, Martinez-Martinez P, Kramer BW, Gavilanes AW.
Fetal asphyctic preconditioning modulates the acute cytokine response thereby protecting against perinatal asphyxia in neonatal rats. J Neuroinflammation. 2013 Jan 26;10(1):14. [Epub ahead of print]

retracted paper.

Douglas Feinstein — 2013-01-29T17:29:41Z

It was brought to our attention that reference #5 (Mandal et al., 2006) which we cited in the first paragraph of the introduction section, was subsequently retracted. We have looked at the data that was retracted, and conclude that data has no direct bearing upon the results we've presented here regarding the effects of sevoflurane on EAE.

Questioning Caffeine/Alzheimer's Connection

Jeana Thomas — 2010-09-24T16:00:35Z

I simply have this question: How do we then explain the rampant Alzheimer's and other BBB diseases in the U.S. which is so universally addicted to caffeine?

geographic tongue relevant to brain autoimmunity?

Kelly Greenberg — 2009-04-14T14:23:28Z

I'm just a mom of an autistic three year old doing some late night reading and read your article. Every time my son regresses, he gets geographic tongue, which is also an autoimmune respose. I haven't read anything about a correlation, I guess that's why I'm mentioning it. Maybe someone will research this. I am sure they are connected in my son's case.

COX-2 inhibition by parecoxib and ischemic brain injury

Eduardo Candelario-Jalil — 2007-01-24T19:29:15Z

It is widely accepted that neuroinflammation is one of the mechanisms known to participate in the evolution of ischemic brain injury. Inhibition of the inducible isoform of cyclooxygenase (COX-2) has been shown to be neuroprotective in several models of brain damage including ischemic stroke. The article by Kelsen et al. provides additional information on the effects of parecoxib (the only COX-2 inhibitor clinically approved for intravenous administration) in an in vivo model of cerebral ischemia in rats. This is the first study to document the beneficial effects of a COX-2 inhibitor using the MRI technology. Interestingly, parecoxib treatment reduced ADC abnormalities one week after ischemia, which indicates, for the first time, the involvement of COX-2 in edema formation following ischemic stroke. Methods are sound and very well described. This study provides an interesting insight into the protective effect of parecoxib, and this report is a good example of how pre-clinical studies should be performed, in order to evaluate the neuroprotective efficacy of new drugs for the treatment of cerebral ischemia.

Oxidative - Redox stress by Beta amyloid may also be true for islet amyloid within pancreatic islets of those patients with metabolic syndrome and type 2 diabetes mellitus.

Melvin Hayden — 2004-11-16T19:30:31Z

Congratulations on an excellent study and the important findings regarding the effect of beta amyloid on lipoprotein oxidation.

We feel the same effect of islet amyloid might be occuring within the islets of the pancreata of patients with metabolic syndrome and type 2 diabetes mellitus. Islet amyloid and beta amyloid share many similar properties (including the polymerization and aggregation induced by free radical polymerization) and it is exciting that the translation of your findings to the islet in regards to hyperamylinemia and islet amyloid within the pancreas may possibly explain the delay in the development of overt type 2 diabetes mellitus with the use of pravastatin in the West of Scotland studies.

Hayden MR, Tyagi SC. Islet Redox Stress: The Manifold Toxicities of Insulin Resistance, Metabolic Syndrome and Amylin Derived Islet Amyloid in Type 2 Diabetes Mellitus. JOP. J Pancreas (Online) 2002; 3(4):86-108

Nicolls MR, D'Antonio JM, Hutton JC, Gill RG, Czwornog JL, Duncan MW. Proteomics as a tool for discovery: proteins implicated in Alzheimer's disease are highly expressed in normal pancreatic islets. J Proteome Res 2003; 2(2):199-205

Keep up the exciting work in this field and again kudos for this great and exciting paper.

Sincerely,

M.R. Hayden, M.D.