Neurotransmitter synthesis by newborn neurons in the penumbral cortex, one step forwards to functional neurogenesis in the poststroke adult brain

• Stroke ranks as the #1 cause of handicapping humans in adult life. Up to date, there is no medication available to cure the post stroke neurological deficits. Fortunately, stroke patients usually experience spontaneous neurologic improvements at various degrees, which start days after a stroke and last up to 18 months. The pathophysiological mechanisms responsible for the post stroke spontaneous recovery are scarcely understood. Endogenous neurogenesis is one of the plausible pathways. In response to an acute ischemic insult, endogenous cells inside the cerebral cortex have been found to be able to divide at as early as 24-48 hours after ischemia to generate daughter neurons in the penumbral cortex, which gives rise to a quick in situ cortical neurogenesis. Meanwhile, the proliferation of neural stem cells in the subventricular zone is augmented after stroke. These stem cells, in addition to following a rostral migrating stream to their routine destination olfactory bulbs, as they usually do under physiological circumstances, start to migrate towards the infarct region. One week after stroke, they arrive at the periinfarct cortex where they differentiate into neurons, which contributes to a late phase cortical neurogenesis. Whether or not newborn neurons may function in the post stroke adult brains is a crucial issue in neurogenesis research. For the newborn neurons to function, one of the fundamental prerequisites is that they must be capable of synthesizing neurotransmitters. To specifically address this question, the biosynthesis of the excitatory neurotransmitter acetylcholine (Ach) and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is examined in adult rat brains after a photothrombotic cortical "ring" stroke with spontaneous reperfusion. To label the newborn brain cells, the DNA duplication marker 5-bromodeoxyuridine (BrdU) is repeatedly injected so that it becomes incorporated into the nuclear DNA while brain cells proliferate. Single/double/triple immunohistochemistry or immunofluorescence is performed to detect possible appearances of neurotransmitters, their synthesizing enzymes and the nuclear BrdU incorporation. As early as 48 hours after a stroke, the neurotransmitters Ach and GABA are detected inside the cytoplasm of the newborn neurons in the ischemic penumbral cortex. These cholinergic and GABAergic neurons survive up to 90 days in the post stroke cortex. In addition, choline acetyl transferase (ChAT) and glutamic acid decarboxylase (GAD), which are the substrate enzymes essential for the biosynthesis of Ach and GABA, are also identified in the BrdUimmunolabelled newborn neurons. As analysed by 3-D confocal microscopy, the neurotransmitters are colocalized with the neuron-specific marker NeuN in the same cells while they exhibit BrdU-immuno-labelling in their nuclei, which confirms their neuronal identity. These data suggest that the newborn neurons in the penumbral cerebral cortex are capable of synthesizing the neurotransmitter Ach and GABA, which makes one fundamental step forwards to a functional neurogenesis in the post stroke adult brains.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

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