DN2M » Towards the development of new diagnostic and treatment strategies for hypothalamic-related diseases

Towards the development of new diagnostic and treatment strategies for hypothalamic-related diseases

The hypothalamus is the part of the diencephalon located below the thalamus; it lies along the walls of the third ventricle below the hypothalamic sulcus and continues across the floor of the ventricle.

Despite its small size (4 g), no other brain structure contains so many specialized cell groups. The hypothalamus controls vital bodily processes including cardiovascular regulation, sleep, metabolism, stress, thermoregulation, water and electrolyte balance, appetite regulation, sexual behavior and endocrine and immune responses. All these functions are related to affective and emotional behavior. The wide range of tasks controlled by a very small part of the brain makes the hypothalamic region particularly prone to involvement in several disorders.

Significantly, the human hypothalamus has been implicated in homeostatic and developmental disorders, including sudden infant death syndrome, Prader-Willi syndrome, disturbance of biological rhythms, infertility, and diabetes and obesity, as well as in episodic brain disorders such as migraine, depression, narcolepsy and cluster headaches. Functional stereotactic neurosurgery of the hypothalamus is currently used for the treatment of cluster headaches, and has recently been shown to have beneficial effects in the treatment of paroxysmal ophthalmic pain in multiple sclerosis patients. Excitingly, it has also been shown to activate neural activity in cognitive and memory circuits in patients with mild Alzheimer’s disease.

By providing new insights into the anatomy and the function of the human hypothalamus, our research should be useful both in developing new treatment strategies involving functional stereotactic surgery, as well as in the morphological and functional inspection of the hypothalamus of patients with hypothalamus-related disorders in everyday clinical practice. 

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Measurement of brownian motion of water molecules using diffusion MRI in male and female volunteers at two stages of the artificial ovarian cycle.

a: Anatomical specification of the voxel (sampling volume) chosen in this study. In a given tissue, when the space between cells is relatively large (b), water molecules are free to move from one voxel to another (c). Upon application of the second gradient the spin of hydrogen nuclei of displaced water molecules are not in phase. This results in a high apparent diffusion coefficient (ADC) that is coded as hypersignal displayed in clear grey. Conversely, when the space between the cells is relatively small (d), water molecules are densely packed allowing the spins of hydrogen nuclei to be in phase. This results in a low ADC that is coded as hyposignal displayed in dark grey (e). f: ADC mapping of the brain in coronal view with highlighted regions of interest (CSF of the lateral ventricles and mediobasal hypothalamus) where ADC is measured. g: T1-weighted MRI in the same plane identifying anatomical landmarks (LV: lateral ventricle; ic: internal capsule; 3V: third ventricle; ARH: arcuate nucleus of the hypothalamus; opt: optic tract).  h: Box plot representation of the ratio of hypothalamic ADC/cerebrospinal fluid (CSF) ADC values measured in women (n=10) at two stages of their artificial menstrual cycle (d-2: 2 days before use of oral contraception in the pill-free interval; d13, 13 days after initiating oral contraception) and in men (n = 10). These MRI-based physiological studies, which yield insights into the neural processes that respond to sex steroid hormones to regulate reproduction in humans, may pave the way for the development of new diagnostic and treatment strategies in the central loss of reproductive competence in human syndromes, such as hypothalamic amenorrhea.

Adapted from Baroncini et al., Neuroimage 50:428-433, 2010 and Prevot et al., Frontiers in Neuroendocrinology 31:241-258, 2010.