Erratum to: Pomalidomide mitigates neuronal loss, neuroinflammation, and behavioral impairments induced by traumatic brain injury in rat

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6′-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.

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NEURONAL LOSS AND CYTOSKELETAL PERTURBATION AFTER TRAUMATIC BRAIN INJURY (TBI) IN THE NFH/LacZ TRANSGENIC MOUSE

Journal of Neuropathology & Experimental Neurology ◽

10.1097/00005072-199805000-00039 ◽

1998 ◽

Vol 57 (5) ◽

pp. 475

Author(s):

J. E. Galvin ◽

V. M. -Y. Lee ◽

M. Nakamura ◽

K. E. Saatman ◽

R. Raghupathi ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Transgenic Mouse ◽

Neuronal Loss

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Deletion of Mst1 attenuates neuronal loss and improves neurological impairment in a rat model of traumatic brain injury

Brain Research ◽

10.1016/j.brainres.2017.10.018 ◽

2018 ◽

Vol 1688 ◽

pp. 15-21 ◽

Cited By ~ 6

Author(s):

Di Li ◽

Haibo Ni ◽

Qin Rui ◽

Rong Gao ◽

Gang Chen

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Rat Model ◽

Neuronal Loss ◽

Neurological Impairment

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Enhancement of Neurogenesis and Memory by a Neurotrophic Peptide in Mild to Moderate Traumatic Brain Injury

Neurosurgery ◽

10.1227/neu.0000000000000577 ◽

2014 ◽

Vol 76 (2) ◽

pp. 201-215 ◽

Cited By ~ 18

Author(s):

Muhammad Omar Chohan ◽

Olga Bragina ◽

Syed Faraz Kazim ◽

Gloria Statom ◽

Narjes Baazaoui ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Dentate Gyrus ◽

Parietal Cortex ◽

Saline Solution ◽

Neuronal Loss ◽

Synaptic Density ◽

Moderate Traumatic Brain Injury ◽

Long Term Treatment ◽

Newborn Neurons

ABSTRACT BACKGROUND: Traumatic brain injury (TBI) is a risk factor for Alzheimer disease (AD), a neurocognitive disorder with similar cellular abnormalities. We recently discovered a small molecule (Peptide 6) corresponding to an active region of human ciliary neurotrophic factor, with neurogenic and neurotrophic properties in mouse models of AD and Down syndrome. OBJECTIVE: To describe hippocampal abnormalities in a mouse model of mild to moderate TBI and their reversal by Peptide 6. METHODS: TBI was induced in adult C57Bl6 mice using controlled cortical impact with 1.5 mm of cortical penetration. The animals were treated with 50 nmol/d of Peptide 6 or saline solution for 30 days. Dentate gyrus neurogenesis, dendritic and synaptic density, and AD biomarkers were quantitatively analyzed, and behavioral tests were performed. RESULTS: Ipsilateral neuronal loss in CA1 and the parietal cortex and increase in Alzheimer-type hyperphosphorylated tau and A-β were seen in TBI mice. Compared with saline solution, Peptide 6 treatment increased the number of newborn neurons, but not uncommitted progenitor cells, in dentate gyrus by 80%. Peptide 6 treatment also reversed TBI-induced dendritic and synaptic density loss while increasing activity in tri-synaptic hippocampal circuitry, ultimately leading to improvement in memory recall on behavioral testing. CONCLUSION: Long-term treatment with Peptide 6 enhances the pool of newborn neurons in the dentate gyrus, prevents neuronal loss in CA1 and parietal cortex, preserves the dendritic and synaptic architecture in the hippocampus, and improves performance on a hippocampus-dependent memory task in TBI mice. These findings necessitate further inquiry into the therapeutic potential of small molecules based on neurotrophic factors.

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Mesenchymal stem cell therapy for the treatment of traumatic brain injury: progress and prospects

Reviews in the Neurosciences ◽

10.1515/revneuro-2019-0002 ◽

2019 ◽

Vol 30 (8) ◽

pp. 839-855 ◽

Cited By ~ 10

Author(s):

Mahasweta Das ◽

Karthick Mayilsamy ◽

Shyam S. Mohapatra ◽

Subhra Mohapatra

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neuronal Damage ◽

Neuronal Loss ◽

Tumor Formation ◽

Functional Improvement ◽

Preclinical Research ◽

Mortality And Morbidity ◽

Mesenchymal Stem Cell Therapy ◽

Beneficial Effects

Abstract Traumatic brain injury (TBI) is a major cause of injury-related mortality and morbidity in the USA and around the world. The survivors may suffer from cognitive and memory deficits, vision and hearing loss, movement disorders, and different psychological problems. The primary insult causes neuronal damage and activates astrocytes and microglia which evokes immune responses causing further damage to the brain. Clinical trials of drugs to recover the neuronal loss are not very successful. Regenerative approaches for TBI using mesenchymal stem cells (MSCs) seem promising. Results of preclinical research have shown that transplantation of MSCs reduced secondary neurodegeneration and neuroinflammation, promoted neurogenesis and angiogenesis, and improved functional outcome in the experimental animals. The functional improvement is not necessarily related to cell engraftment; rather, immunomodulation by molecular factors secreted by MSCs is responsible for the beneficial effects of this therapy. However, MSC therapy has a few drawbacks including tumor formation, which can be avoided by the use of MSC-derived exosomes. This review has focused on the research works published in the field of regenerative therapy using MSCs after TBI and its future direction.

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Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study

Critical Care ◽

10.1186/s13054-020-03373-9 ◽

2020 ◽

Vol 24 (1) ◽

Author(s):

Rita Campos-Pires ◽

Haldis Onggradito ◽

Eszter Ujvari ◽

Shughoofa Karimi ◽

Flavia Valeo ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Outcome ◽

Neuroprotective Effect ◽

Neuronal Loss ◽

Brain Trauma ◽

Lesion Volume ◽

Oxygen Balance ◽

Sprague Dawley ◽

Locomotor Deficits

Abstract Background Traumatic brain injury (TBI) is a major cause of morbidity and mortality, but there are no clinically proven treatments that specifically target neuronal loss and secondary injury development following TBI. In this study, we evaluate the effect of xenon treatment on functional outcome, lesion volume, neuronal loss and neuroinflammation after severe TBI in rats. Methods Young adult male Sprague Dawley rats were subjected to controlled cortical impact (CCI) brain trauma or sham surgery followed by treatment with either 50% xenon:25% oxygen balance nitrogen, or control gas 75% nitrogen:25% oxygen. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24 h after injury. Histological outcomes were assessed following perfusion fixation at 15 min or 24 h after injury or sham procedure. Results Xenon treatment reduced lesion volume, reduced early locomotor deficits, and attenuated neuronal loss in clinically relevant cortical and subcortical areas. Xenon treatment resulted in significant increases in Iba1-positive microglia and GFAP-positive reactive astrocytes that was associated with neuronal preservation. Conclusions Our findings demonstrate that xenon improves functional outcome and reduces neuronal loss after brain trauma in rats. Neuronal preservation was associated with a xenon-induced enhancement of microglial cell numbers and astrocyte activation, consistent with a role for early beneficial neuroinflammation in xenon’s neuroprotective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma.

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Guanosine Protects Against Traumatic Brain Injury-Induced Functional Impairments and Neuronal Loss by Modulating Excitotoxicity, Mitochondrial Dysfunction, and Inflammation

Molecular Neurobiology ◽

10.1007/s12035-016-0238-z ◽

2016 ◽

Vol 54 (10) ◽

pp. 7585-7596 ◽

Cited By ~ 16

Author(s):

Rogério da Rosa Gerbatin ◽

Gustavo Cassol ◽

Fernando Dobrachinski ◽

Ana Paula O. Ferreira ◽

Caroline B. Quines ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mitochondrial Dysfunction ◽

Neuronal Loss ◽

Functional Impairments

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Animal Models of Traumatic Brain Injury: Is There an Optimal Model That Parallels Human Brain Injury?

Annual Review of Nursing Research ◽

10.1891/0739-6686.33.31 ◽

2015 ◽

Vol 33 (1) ◽

pp. 31-73 ◽

Cited By ~ 7

Author(s):

Teresita L. Briones

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Animal Models ◽

Clinical Setting ◽

Preclinical Studies ◽

Mortality And Morbidity ◽

High Prevalence ◽

Neuroprotective Strategies ◽

Behavioral Impairments ◽

Underlying Pathophysiology

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in the younger population worldwide. Survivors of TBI often experience long-term disability in the form of cognitive, sensorimotor, and affective impairments. Despite the high prevalence in, and cost of TBI to, both individuals and society, some of its underlying pathophysiology is not completely understood. Animal models have been developed over the past few decades to closely replicate the different facets of TBI in humans to better understand the underlying pathophysiology and behavioral impairments and assess potential therapies that can promote neuroprotection. However, no effective treatment for TBI has been established to date in the clinical setting, despite promising results generated in preclinical studies in the use of neuroprotective strategies. The failure to translate results from preclinical studies to the clinical setting underscores a compelling need to revisit the current state of knowledge in the use of animal models in TBI.

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