For decades researchers thought that the production of neurons stopped early in life, leaving the adult brain with a finite number of neurons. The discovery of neural stem cells with self-renewing capacity and multi-potency has radically changed this view, and it is now well accepted that the birth of new neurons continues throughout adulthood. Adult neurogenesis occurs in two primary locations: the olfactory bulb and the central part of the hippocampus, called the dendate gyrus (shown at the left).
Image: Widefield multi-photon fluorescence image of a rat hippocampus stained to reveal the distribution of glia (cyan), neurofilaments (green) and cell nuclei (yellow). The image was produced as part of an ongoing brain mapping project for the Whole Brain Catalog.
The human brain in cross section
Peering deeply – and quite literally – into the intact brain: A video fly-through
CLARITY, pioneered by Stanford psychiatrist/bioengineer Karl Deisseroth, MD, PhD, renders intact tissue samples transparent. Above is a video clip showing off the new method’s capabilities. First you’ll witness a “fly-through” of a complete mouse brain using fluorescent imaging. The immediately following clip – it’s spectacular! – provides a three-dimensional view of a mouse hippocampus (the brain’s brain’s memory hub), with projecting neurons depicted in green, connecting interneurons in red, and layers of support cells, or glia, in blue.
Note that in both cases, there was no need to slice the tissue into ultra-thin sections, analyze them chemically and/or optically and then laboriously “sew” them back together via computer algorithms in order to reconstruct a 3-D virtual image of the biological sample. All that was required, after performing the necessary hocus-pocus, was to ”send in the stain” (i.e., use histochemical means to paint different cell types different colors) and move the sample or camera lens or shift the latter’s focal length. Nice trick. With big implications for biomedical research.
Purkinje neurons play an essential role in motor function. Here the Purkinje neurons reach their arbor-like dendrites into the molecular layer of the developing cerebellum of a mouse. The mostly green cells at the bottom left are cerebellar granule cells, which relay information from the nervous system to the Purkinje neurons.
The Human Brain in cross section (near the midline)
The following structures can be located here:
Cerebellum, 4th ventricle, Superior colliculus, Inferior colliculus, Periaqueductal gray, Pons, Dorsal funiculus, MLF, Medial lemniscus, Red nucleus, Mammillary body, Pineal body, Posterior commissure, Anterior commissure, Thalamus, and Fornix.
In the hippocampus, neural stem cells (green) sit in a layer below their progeny, the granule neurons (red). When activated by extrinsic stimuli, they enter mitosis and generate neuron progenitor cells, which eventually mature into neurons and migrate into the layer above. The number of neural stem cells in the hippocampus decreases over time, possibly contributing to the cognitive impairment associated with aging. One hypothesis is that, after a rapid series of divisions, these neural stem cells disappear via their conversion into astrocytes.
Image: Section of a mouse hippocampus imaged with Zeiss LSM 50 confocal microscope with a 40X C-Apochromat water-immersion objective lens (N.A. value 1.2, working distance 220 microns) at 62x magnification. Brain slices were fixed in 4% paraformaldehyde, immunolabeled, and then cleared in FocusClear (CelExplorer, Taiwan).
Stem cells grow to become human neurons
“In neurodegenerative disorders, such as Parkinson’s and Huntington’s disease, selective loss of some 500,000 cells in critical brain regions can lead to devastating symptoms,” writes Dr. Ole Isacson, Director of the Neuroregeneration Laboratory at McLean Hospital.
Our understanding of regeneration and plasticity in the mammalian nervous system has developed greatly through basic research following implantation of fetal stem or genetically engineered cells into the adult brain. While the adult brain previously was thought of as a non-regenerative system for pathway formation, recent studies show how dissociated primordial neurons and stem cells implanted into the adult central nervous system can grow to reconnect neuronal pathways and integrate in a molecular and physiological fashion.
Neurodegenerative diseases have very few effective treatments, which is why the laboratory’s research team is working towards a new understanding of these diseases by studying the regenerative properties of stem cells.
MCA aneurysm - right pterional approach
Cerebral aneurysm is a dilatation of the cerebral blood vessels of various etiology probably due to the different structure of cerebral vessels (less elasticity, less muscle, thinner adventitia) and the absence of little connective tissue around the artery.