Distinct vasopressin content in the hypothalamic supraoptic and paraventricular nucleus of rats exposed to low and high ambient temperature.

Both high and low ambient temperature represent thermal stressors that, among other physiological responses, induce activation of the hypothalamic-pituitary-adrenal (HPA) axis and secretion of arginine-vasopressin (AVP). The exposure to heat also leads to disturbance of osmotic homeostasis. Since AVP, in addition to its well-known peripheral effects, has long been recognized as a hormone involved in the modulation of HPA axis activity, the aim of the present study was to elucidate the hypothalamic AVP amount in the acutely heat/cold exposed rats. Rats were exposed to high (+38°C) or low (+4°C) ambient temperature for 60min. Western blot was employed for determining hypothalamic AVP levels, and the difference in its content between supraoptic (SON) and paraventricular nucleus (PVN) was detected using immunohistochemical analysis. The results showed that exposure to both high and low ambient temperature increased hypothalamic AVP levels, although the increment was higher under heat conditions. On the other hand, patterns of AVP level changes in PVN and SON were stressor-specific, given that exposure to cold increased the AVP level in both nuclei, while heat exposure affected the PVN AVP content alone. In conclusion, our results revealed that cold and heat stress influence hypothalamic AVP amount with different intensity. Moreover, different pattern of AVP amount changes in the PVN and SON indicates a role of this hormone not only in response to heat as an osmotic/physical threat, but to the non-osmotic stressors as well.

Molecular imaging of brain lipid environment of lymphocytes in amyotrophic lateral sclerosis using magnetic resonance imaging and SECARS microscopy.

This paper highlights some of the key technologies of using two innovative molecular imaging modalites, magnetic resonance imaging (MRI) and nonlinear optical microscopy, for imaging intravenously injected ultra small paramagnetic iron oxide nanoparticles cross linked with antibodies (CLUSPIO) in the amyotrophic lateral sclerosis (ALS) experimental model in vivo or ex vivo, respectively. Intensive efforts have been made in investigating the causes of abnormalities in lipid metabolism, monitored in some neurodegenerative disorders systems. It has been shown that an abnormal accumulation of some common lipids in motor nerve cells may play a critical role in the development of amyotrophic lateral sclerosis. The presented experiments were performed on brain specimens from the transgenic rat model expressing multiple copies of mutated (G93A) human SOD-1 gene, after CD4+ lymphocytes were magnetically labeled with i.v.i. CLUSPIO antibodies. In vivo MRI revealed marked signal intensity enhancements in specific pathological regions of the ALS rat brain as compared to the wild type. Surface-enhanced coherent anti-Stokes Raman scattering (SECARS) microscopy indicated cellular interactions based on lipids association to anti-CD4 CLUSPIO.

Imaging cellular markers of neuroinflammation in the brain of the rat model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder affecting upper and lower motoneurons. Since immune disbalance is known to be an important manifestation of the disease, working with the familial ALS rat model, hSODG93A (containing multiple copies of the human SOD1 G93A mutation), we were particularly interested in following by live magnetic resonance imaging (MRI) the immune cells labeled by ultra small paramagnetic iron oxide (USPIO) nanoparticles. In addition, microglial activation was studied by immunocytochemistry. MRI of USPIO labeled Tcells revealed CD4+ lymphocyte infiltration in the midbraininterbrain region while the CD8+ cells were more confined to the brainstem region. By way of gadolinium (Gd) contrast it was also confirmed that the bloodbrain barrier (BBB) was compromised. Moreover, it was revealed that the regions of BBB breakthrough were congruent with the MRI foci of Tcell infiltration. Immunocytochemistry revealed microglial activation and fusion, possibly phagocytic interactions with neurons in the hippocampus and brainstem. These observations prove the existence of an elaborate inflammatory process in the brain of hSODG93A rats, and also demonstrates the complexity and multifocality of ALS as having its inflammatory manifestations also in the central nervous system (hippocampus) distinct from clinically described motor foci of degeneration.