Microglia replacement therapy helps treat people with a rare genetic condition called ALSP, suggesting the approach could also work for other neurological disorders like Alzheimer’s
Category: neuroscience
Catalase Activity in the Brain Is Associated with Recovery from Brain Injury in a Piglet Model of Traumatic Brain Injury
Background/Objectives: Traumatic brain injury (TBI) is a global leading cause of disability and death, with millions of new cases added each year. Oxidative stress significantly exacerbates primary TBI, leading to increased levels of intracerebral cell death, tissue loss, and long-term functional deficits in surviving patients. Catalase and superoxide dismutase (SOD) mitigate oxidative stress and play a critical role in dampening injury severity. This study examines the neuroprotective effects of the novel antioxidant alpha lipoic acid-based therapeutic, CMX-2043, on antioxidant enzymes in a preclinical TBI model via various drug administration routes. Methods: Piglets (n = 28) underwent cortical controlled impact to induce moderate–severe TBI and were assigned to placebo (n = 10), subcutaneous CMX-2043 (SQ, 10 mg/kg; n = 9), or intravenous CMX-2043 (IV, 9 mg/kg; n = 9) treatment groups. Treatments began 1 h after TBI induction and continued for 5 days. MRI was performed throughout the study period to evaluate brain recovery. Blood was collected at 1, 7, and 42 days post-TBI, and liver and brain tissues were collected at 42 days post-TBI to measure catalase and SOD activity. Results: CMX-2043 IV-treated piglets showed 46.3% higher hepatic catalase activity than placebo (p = 0.0038), while the SQ group did not show significant changes in hepatic catalase activity compared to placebo. In the brain, SQ-treated piglets had significantly higher catalase activity than both IV (p = 0.0163) and placebo (p = 0.0003) groups (45.8340 ± 3.0855, 36.4822 ± 1.5558, 31.6524 ± 1.3129 nmol/min/mg protein for SQ, IV, and placebo, respectively), while IV-treated piglets did not show significant changes compared to placebo. IV-treated piglets did exhibit 39.3% higher brain SOD activity than placebo (p = 0.0148), while the SQ group did not show a significant change. CMX-2043 treatment did not alter plasma antioxidant enzyme activity during the study period. Importantly, within CMX-2043 treated TBI groups, piglets with significantly decreased lesion volumes, midline shift, and combined swelling and atrophy had better brain recovery, determined by MRI on day 1, 7, and 42 days post-injury TBI, exhibited higher brain catalase activity at 42 days post-injury TBI regardless of administration route, suggesting a link between improved recovery and sustained local catalase activity. Conclusions: This study highlights the impact of administration route on tissue-specific antioxidant responses, with IV administration enhancing liver catalase and brain SOD activity, while SQ administration primarily elevated brain catalase activity. In addition, this study shows an association between increased brain catalase activity and decreased TBI brain lesioning, midline shift, and combined swelling and atrophy, thus emphasizing the role of antioxidant defenses in neuroprotection post-injury.
A quantitative theory unlocks the mysteries of why we sleep
Comparing our findings across species with those across growth led us to a final question. If the purpose of sleep shifts from being about neural reorganisation as children to being about repair once we’re grown, when exactly does that transition occur, and how sudden is it? Armed with our new theory plus human developmental data, we could answer this question with surprising accuracy: the transition occurs when we’re extremely young – at about 2.5 years of age – and it happens extremely abruptly, like water freezing at 0°C.
We were delighted with this stunning result. First, it gave us an even greater appreciation for the critical importance of sleep: never again would we underestimate its importance for our children, especially in their first few years of life when their sleep is doing something so fundamentally different and extraordinarily important, something that seemingly can’t be made up for later in life. Second, we had discovered that these two states of sleep, while they looked remarkably similar from the outside, are actually analogous to completely different states of matter before and after the stark dividing line of 2.5 years of age. Before 2.5 years, our brains are more fluid and plastic, enabling us to learn and adapt quickly, similar to the state of water flowing around obstacles. After 2.5 years, our brains are much more crystalline and frozen, still capable of learning and adapting but more like glaciers slowly pushing across a landscape.
Many questions still remain. How much does sleep vary across humans and across species? Can this early fluid phase of sleep be extended? Is this phase already extended or shortened in some individuals, and what costs or benefits are associated with that? What other functions of sleep have piggybacked on to the primary functions of repair and neural reorganisation? How do the different reasons for sleep compete for or share sleep time, either across ages or even within a single night? It will take much more work to fully unravel the mysteries of sleep, but our recent insights – about age-based shifts in the purpose of sleep and the mathematical, predictive theories that quantify them – represent an essential tool to plumb these depths even further.
Michael Levin: How would you test for consciousness?
Joscha Bach (Executive Director) and Lou de K (VP of Programs) interview our scientific advisor Michael Levin on how he would go about testing for consciousness.
Looking to study neurological conditions, researchers produce over 400 different types of nerve cells
Nerve cells are not just nerve cells. Depending on how finely we distinguish, there are several hundred to several thousand different types of nerve cells in the human brain, according to the latest calculations. These cell types vary in their function, in the number and length of their cellular appendages, and in their interconnections. They emit different neurotransmitters into our synapses, and depending on the region of the brain—for example, the cerebral cortex or the midbrain—different cell types are active.
When scientists produced nerve cells from stem cells in Petri dishes for their experiments in the past, it was not possible to take their vast diversity into account. Until now, researchers had only developed procedures for growing a few dozen different types of nerve cell in vitro. They achieved this using genetic engineering or by adding signaling molecules to activate particular cellular signaling pathways. However, they never got close to achieving the diversity of hundreds or thousands of different nerve cell types that actually exist.
“Neurons derived from stem cells are frequently used to study diseases. But up to now, researchers have often ignored which precise types of neuron they are working with,” says Barbara Treutlein, Professor at the Department of Biosystems Science and Engineering at ETH Zurich in Basel.
People with ‘young brains’ outlive ‘old-brained’ peers, Stanford Medicine scientists find
A blood-test analysis developed at Stanford Medicine can determine the “biological ages” of 11 separate organ systems in individuals’ bodies and predict the health consequences.