scholarly journals Molecular neuroimaging of inflammation in HIV

Author(s):  
Jasmini Alagaratnam ◽  
Alan Winston

Abstract People-with-HIV now have near-normal life expectancies due to the success of effective combination antiretroviral therapy (cART). Following cART initiation, immune recovery occurs, and opportunistic diseases become rare. Despite this, high rates of non-infectious comorbidities persist in treated people-with-HIV, hypothesised to be related to persistent immuno-activation. One such comorbidity is cognitive impairment, which may partly be driven by ongoing neuro-inflammation in otherwise effectively-treated people-with-HIV. In order to develop therapeutic interventions to address neuro-inflammation in effectively-treated people-with-HIV, a deeper understanding of the pathogenic mechanisms driving persistent neuro-inflammatory responses and the ability to better characterise and measure neuro-inflammation in the central nervous system is required. This review highlights recent advances in molecular neuroimaging techniques which have the potential to assess neuro-inflammatory responses within the central nervous system in HIV-disease. Proton magnetic resonance spectroscopy ( 1H-MRS) has been utilised to assess neuro-inflammatory responses since early in the HIV pandemic and shows promise in recent studies assessing different antiretroviral regimens. 1H-MRS is widely available in both resource-rich and some resource-constrained settings and is relatively inexpensive. Brain positron emission tomography (PET) imaging using Translocator Protein (TSPO) radioligands is a rapidly evolving field; newer TSPO-radioligands have lower signal-to-noise ratio and have the potential to localise neuro-inflammation within the brain in people-with-HIV. As HIV therapeutics evolve, people-with-HIV continue to age and develop age-related comorbidities including cognitive disorders. The use of novel neuroimaging modalities in the field is likely to advance in order to rapidly assess novel therapeutic interventions and may play a role in future clinical assessments.

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 437 ◽  
Author(s):  
Edoardo Parrella ◽  
Vanessa Porrini ◽  
Marina Benarese ◽  
Marina Pizzi

Mast cells (MCs) are densely granulated perivascular resident cells of hematopoietic origin. Through the release of preformed mediators stored in their granules and newly synthesized molecules, they are able to initiate, modulate, and prolong the immune response upon activation. Their presence in the central nervous system (CNS) has been documented for more than a century. Over the years, MCs have been associated with various neuroinflammatory conditions of CNS, including stroke. They can exacerbate CNS damage in models of ischemic and hemorrhagic stroke by amplifying the inflammatory responses and promoting brain–blood barrier disruption, brain edema, extravasation, and hemorrhage. Here, we review the role of these peculiar cells in the pathophysiology of stroke, in both immature and adult brain. Further, we discuss the role of MCs as potential targets for the treatment of stroke and the compounds potentially active as MCs modulators.


2007 ◽  
Vol 65 (1) ◽  
pp. 167-169
Author(s):  
André Palma da Cunha Matta ◽  
Márcia de Castro Diniz Gonsalves

Congenital muscle dystrophy (CMD) is a heterogeneous group of autosomal recessive myopathies. It is known that CMD may affect the central nervous system (CNS). Some authors have shown that merosin-negative CMD patients may have encephalic metabolic disturbances. In order to study metabolic changes within the brain, the authors performed a magnetic resonance spectroscopy (MRS) study in a 1-year-old girl with merosin-positive CMD (MP-CMD). MRS of brain demonstrated that NAA/Cr ratio was decreased (1.52), while Cho/Cr ratio was increased (1.78). These findings suggest that metabolic changes in CNS can also be found in patients with MP-CMD.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Peiqing Chen ◽  
Wenjuan Zhao ◽  
Yanjie Guo ◽  
Juan Xu ◽  
Ming Yin

CX3C chemokine ligand 1 (CX3CL1) is an intriguing chemokine belonging to the CX3C family. CX3CL1 is secreted by neurons and plays an important role in modulating glial activation in the central nervous system after binding to its sole receptor CX3CR1 which mainly is expressed on microglia. Emerging data highlights the beneficial potential of CX3CL1-CX3CR1 in the pathogenesis of Alzheimer’s disease (AD), a common progressive neurodegenerative disease, and in the progression of which neuroinflammation plays a vital role. Even so, the importance of CX3CL1/CX3CR1 in AD is still controversial and needs further clarification. In this review, we make an attempt to present a concise map of CX3CL1-CX3CR1 associated with AD to find biomarkers for early diagnosis or therapeutic interventions.


2007 ◽  
Vol 107 (4) ◽  
pp. 873-877 ◽  
Author(s):  
Takaaki Beppu ◽  
Takashi Inoue ◽  
Hideaki Nishimoto ◽  
Shinichi Nakamura ◽  
Yoichi Nakazato ◽  
...  

✓Primary granulomatous angiitis of the central nervous system (CNS) is extremely rare. Its preoperative diagnosis is difficult as the condition displays nonspecific features on routine neuroimaging investigations. In this paper, the authors report findings of magnetic resonance (MR) spectroscopy and fractional anisotropy (FA) with diffusion tensor MR imaging in a case of granulomatous angiitis of the CNS. A 30-year-old man presented with morning headaches and grand mal seizures. An MR image revealed a mass resembling glioblastoma in the right temporal lobe. Magnetic resonance spectroscopy showed a high choline/creatine (Cho/Cr) ratio indicative of a malignant neoplasm, accompanied by a slight elevation of glutamate and glutamine. The FA value was very low, which is inconsistent with malignant glioma. The mass was totally removed surgically. Histologically, the peripheral lesion of the mass consisted of a rough accumulation of fat granule cells, infiltration of inflammatory cells, and distribution of capillary vessels. Some vessels within the lesion were replaced by granulomas. The histological diagnosis was granulomatous angiitis of the CNS. The MIB-1–positive rate of the granuloma was approximately 5%. Both MR spectroscopy and FA were unable to accurately diagnose granulomatous angiitis of the CNS prior to surgery; however, elevated Cho/Cr and glutamate and glutamine shown by MR spectroscopy may indicate the moderate proliferation potential of the granuloma and the inflammatory process, respectively, in this condition. Although the low FA value in the present case enabled the authors to rule out a diagnosis of glioblastoma, FA values in inflammatory lesions require careful interpretation.


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