The latest from http://brainblogger.com!
As usual, here’s our monthly roundup of the best and worst news I came across. July brought us some important findings, namely in the understanding of the mechanisms of different diseases. These are personal opinions, presented in no particular order and we welcome your comments and suggestions. If you have come across interesting studies, let us know in the comment section.
A new therapeutic agent for aneurysmal rupture prevention
Basic research on an animal model of spontaneous aneurysmal rupture has revealed a new potential therapeutic agent. The study published in the Journal of Cerebral Blood Flow and Metabolism evaluated whether Angiotensin-(1-7) could reduce spontaneous aneurysmal subarachnoid hemorrhage. This peptide is known to be able to regulate vascular inflammation and remodeling, important processes in the pathophysiology of intracranial aneurysms.
Treatment with Angiotensin-(1-7) significantly reduced the rupture rate of intracranial aneurysms without affecting the overall incidence of aneurysms. These findings indicate that Angiotensin-(1-7) can be helpful in the prevention of aneurysmal rupture.
Improved treatment for glioblastoma
Glioblastomas are highly malignant tumors that arise from astrocytes – glial cells that are part of the supportive tissue of the brain. Angiotensin-II inhibitors have been reported to reduce angiogenesis and tumour growth in several tumour models. In a study published in the European Journal of Neurology, the effect of Angiotensin-II inhibitors, in addition to the standard radiotherapy and temozolomide (TMZ) therapy, in the clinical outcome of glioblastoma patients was investigated.
The authors found that the number of patients who remained functionally independent at six months after radiotherapy was higher in the group of patients treated with Angiotensin-II inhibitors. The survival rate was also increased. This study therefore shows that the addition of Angiotensin-II inhibitors to radiotherapy and TMZ treatment might improve clinical outcome in glioblastoma patients.
Memory impairment in Alzheimer’s disease may be due to sleep disruption
The exact mechanisms of memory impairment in Alzheimer’s disease are still being unraveled. Beta-amyloid accumulation has been associated with both non-rapid eye movement (NREM) sleep disruption and memory impairment in older adults. It is therefore possible that beta-amyloid pathology may influence hippocampus-dependent memory through impairment of NREM sleep and the associated overnight memory consolidation.
A study published in Nature Neuroscience tested this hypothesis and showed that beta-amyloid correlates significantly with the severity of impairment in NREM sleep, which in turn was further associated with impaired overnight memory consolidation. They also showed that the association between beta-amyloid pathology and impaired memory consolidation was not direct, but dependent on the disrupted NREM sleep. This study therefore shows that sleep disruption is a pathway through which beta-amyloid pathology contributes to cognitive decline.
Gene therapy for hearing loss
According to the World Health Organization, about 5% of the world’s population suffers from disabling hearing impairment. Finding ways to treat it is of obvious importance. Genetics is a major cause of deafness, accounting for up to 50% of prelingual deafness worldwide. Therefore, gene therapy targeting the mutant genes associated with the onset of deafness is a highly promising treatment.
A study published in Science Translational Medicine used gene therapy to target hair cells of the mouse cochlea, the sensory receptors of the auditory system. This approach was able to partially restore sensory transduction, auditory brainstem responses, and acoustic startle reflexes hearing. These results indicate that gene therapy may be helpful in restoring auditory function in deaf patients who carry specific mutations, and that it may complement existing technologies such as cochlear implants and hearing aids.
Sex differences in pain – new findings
Sex differences in pain sensitivity are a matter of growing scientific and clinical interest. One of the mechanisms that strongly contribute to chronic pain hypersensitivity is microglia-to-neuron signaling.
A study published in Nature Neuroscience reached an important conclusion regarding the differential regulation of pain in male and female mice. The authors found that pain hypersensitivity in male and female mice is differentially dependent on microglia and T cells: microglial cells were not required for mechanical pain hypersensitivity in female mice, which actually achieved similar levels of pain hypersensitivity using T lymphocytes. A sex-specific response to microglia-targeted pain treatments was also described.
An important consequence of this finding is the awareness that pain research on male mice may lead to conclusions that do not apply to females. Also, these sex differences should also be taken into account in the clinical practice.
Early mobilization after stroke may not be helpful after all
Early mobilization after stroke is recommended in many guidelines, but the evidence of its efficacy has been scarce. Hence, between 2006 and 2014, the AVERT Trial Collaboration group assessed the effect of early mobilization in patients with ischemic or hemorrhagic stroke in 56 acute stroke units in five countries.
A study published in The Lancet aimed to compare the effectiveness of very early mobilization (within 24h) with usual care after stroke. The group hypothesized that more intensive and early activity would improve functional outcome, reduce complications, and accelerate recovery. But none of this was verified. In fact, fewer patients in the very early mobilization group had a favorable outcome than those in the usual care group. So, although early mobilization after stroke is recommended in many guidelines worldwide, this study shows that these should probably be revised.
A failed attempt in Parkinson’s disease therapy
Pioglitazone is a drug that held promise for the treatment of Parkinson’s disease. Therefore, a a phase 2 trial published in The Lancet Neurology aimed at assessing the effect of pioglitazone on the progression of Parkinson’s disease. Participants with the diagnosis of early Parkinson’s disease were treated with different doses of pioglitazone or with a placebo.
The study found that pioglitazone was unable to modify progression in early Parkinson’s disease, at least at the doses studied. The study even reported the occurrence of serious adverse events. The authors state that the study of pioglitazone in a larger trial in patients with Parkinson’s disease should not be pursued.
Which came first, tobacco or psychosis?
Schizophrenia patients are known to be more likely to smoke and usually smoke heavily. This association has typically been seen as a form of self-medication. But a systematic review published in The Lancet Psychiatry now challenges this view.
This review gathers evidence to suggest that cigarette smoking might actually be a cause of psychosis. The authors reviewed studies in which rates of smoking were reported in people with psychotic disorders, compared with controls and calculated the difference for age at onset of psychosis and age at initiation of smoking. As expected, they found a connection between smoking and psychosis: daily smokers developed psychotic illness at an earlier age than did non-smokers, and those with psychosis started smoking at an earlier age than did healthy controls. However, these differences were non-significant. Despite this link between smoking and psychosis, this is still a chicken and egg situation. But as the authors state, the possibility of a causal link between tobacco use and psychosis merits further examination.
Diabetes-associated inflammation and cognitive decline
One of the consequences of diabetes is cognitive decline. The mechanisms of this association remain to be understood. Neurology published a study that aimed at investigating the relationships between inflammation, cerebral vasoregulation, and cognitive decline in type 2 diabetes.
After two years of follow-up, participants with type 2 diabetes showed diminished cerebral vasoreactivity associated with a decline in multiple cognitive tasks. Higher serum levels of inflammatory markers were were associated with greater changes in cerebral vasoregulation, suggesting that inflammation, by affecting cerebral blood flow, can accelerates decline in executive function and daily activities performance in older people with type-2 diabetes.
Scientific fraud gets heavily punished
Stories of scientific misconduct are burgeoning and article retractions growing exponentially. The most common consequence of such cases is the forced resignation of those involved. Scientists being sentenced to prison on misconduct charges is not common nor likely. But that’s exactly what happened to a former scientist from Iowa State University, Dong-Pyou Han. He was sentenced for fabricating and falsifying data in HIV vaccine trials. And the punishment was quite heavy. Read about it in Nature News.
Askew C, Rochat C, Pan B, Asai Y, Ahmed H, Child E, Schneider BL, Aebischer P, & Holt JR (2015). Tmc gene therapy restores auditory function in deaf mice. Science translational medicine, 7 (295) PMID: 26157030
AVERT Trial Collaboration group, Bernhardt J, Langhorne P, Lindley RI, Thrift AG, Ellery F, Collier J, Churilov L, Moodie M, Dewey H, & Donnan G (2015). Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial. Lancet (London, England), 386 (9988), 46-55 PMID: 25892679
Chung CC, Pimentel D, Jor’dan AJ, Hao Y, Milberg W, & Novak V (2015). Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes. Neurology, 85 (5), 450-8 PMID: 26156513
Gurillo P, Jauhar S, Murray RM, & MacCabe JH (2015). Does tobacco use cause psychosis? Systematic review and meta-analysis. The Lancet. Psychiatry, 2 (8), 718-25 PMID: 26249303
Januel E, Ursu R, Alkhafaji A, Marantidou A, Doridam J, Belin C, Levy-Piedbois C, & Carpentier AF (2015). Impact of renin-angiotensin system blockade on clinical outcome in glioblastoma. European journal of neurology : the official journal of the European Federation of Neurological Societies PMID: 26053493
Mander BA, Marks SM, Vogel JW, Rao V, Lu B, Saletin JM, Ancoli-Israel S, Jagust WJ, & Walker MP (2015). ?-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nature neuroscience, 18 (7), 1051-7 PMID: 26030850
NINDS Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators (2015). Pioglitazone in early Parkinson’s disease: a phase 2, multicentre, double-blind, randomised trial. The Lancet. Neurology, 14 (8), 795-803 PMID: 26116315
Reardon S (2015). US vaccine researcher sentenced to prison for fraud. Nature, 523(7559):138-9.
Shimada K, Furukawa H, Wada K, Wei Y, Tada Y, Kuwabara A, Shikata F, Kanematsu Y, Lawton MT, Kitazato KT, Nagahiro S, & Hashimoto T (2015). Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 35 (7), 1163-8 PMID: 25757758
Sorge RE, Mapplebeck JC, Rosen S, Beggs S, Taves S, Alexander JK, Martin LJ, Austin JS, Sotocinal SG, Chen D, Yang M, Shi XQ, Huang H, Pillon NJ, Bilan PJ, Tu Y, Klip A, Ji RR, Zhang J, Salter MW, & Mogil JS (2015). Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nature neuroscience, 18 (8), 1081-3 PMID: 26120961
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