Sex-specific cognitive effects of mild traumatic brain injury to the frontal and temporal lobes

Richmond-Hacham, Bar; Izchak, Haim; Elbaum, Tomer; Qubty, Doaa; Bader, Miaad; Rubovitch, Vardit; Pick, Chaim C.G.

doi:10.1016/j.expneurol.2022.114022

Cited by 8 publications

(5 citation statements)

References 46 publications

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“…This is in contrast to our present observations in the mild to moderate TBI mice, where the Rotarod behavior was often only mildly or not affected at 3 days after the impact, but increased over time and became maximal at 14 to 21 days after injury. This is in line with several recent publications which showed the delayed and progressed appearance of different behavioral deficits in TBI, paralleled by diffuse, widespread blood brain barrier dysfunction and inflammatory processes like microglia activation as well as synapse loss throughout the brain [30][31][32][33].…”

Section: Delayed Manifestation Of Impaired Locomotor Performance Afte...supporting

confidence: 92%

Four-parameter analysis in modified Rotarod test for detecting minor motor deficits in mice

Shan,

Maurer,

Schwab

2023

BMC Biol

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Background The Rotarod test with commercial apparatus is widely used to assess locomotor performance, balance and motor learning as well as the deficits resulting from diverse neurological disorders in laboratory rodents due to its simplicity and objectivity. Traditionally, the test ends when rodents drop from the accelerating, turning rod, and the only parameter used commonly is “latency to fall”. The values of individual animals can often vary greatly. Results In the present study, we established a procedure for mice with 4 consecutive days of training with 4 trials per day and modified the testing procedure by placing the mice back on the rod repeatedly after each fall until the trial ends (5 min). Data from the fourth training day as baseline results showed that the second, third and fourth trial were more consistent than the first, probably due to habituation or learning. There was no difference between the second, third and fourth trial, two trials may be sufficient in testing. We also introduced 3 additional read-outs: Longest duration on the rod (s), Maximal distance covered (cm), and Number of falls to better evaluate the motor capacity over the 5 min of testing. We then used this 4-parameter analysis to capture the motor deficits of mice with mild to moderate traumatic brain injuries (by a weight dropping on the skull (Marmarou model)). We found that normalization of data to individual baseline performance was needed to reduce individual differences, and 4 trials were more sensitive than two to show motor deficits. The parameter of Maximal distance was the best in detecting statistically significant long-term motor deficits. Conclusions These results show that by making adjustments to the protocol and employing a more refined analysis, it is possible to expand a widely used routine behavioral test with additional accessible parameters that detect relevant deficits in a model of mild to moderate traumatic brain injury. The modified Rotarod test maybe a valuable tool for better preclinical evaluations of drugs and therapies.

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Section: Delayed Manifestation Of Impaired Locomotor Performance Afte...supporting

confidence: 92%

Four-parameter analysis in modified Rotarod test for detecting minor motor deficits in mice

Shan,

Maurer,

Schwab

2023

BMC Biol

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“…Male patients with a history of mTBI had worsened symptom severity and frequency for most symptoms, particularly for head and cognitive symptoms, whereas females exhibited less overall symptomology but more severe symptom severity and frequency for energy symptoms. These sex-specific findings in symptoms following mTBI are supported by preclinical research stating that males exhibit worsened cognitive symptoms, including memory deficits, following mTBI [ 54 , 55 ]. These findings are further supported by clinical data that also suggest sex-specific differences in cognitive functioning, with males exhibiting worsened memory and language skills, following TBI [ 56 , 57 ].…”

Section: Discussionmentioning

confidence: 77%

Sex-specific antioxidant biomarker depletion in patients with a history of mild traumatic brain injury

Koza,

Grossberg,

Bishop

et al. 2024

Advances in Redox Research

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“…2013; Richmond‐Hacham et al. 2024). Compared with these previous efforts, we adopted a configuration that includes an IR‐lucent shelter, two waterspouts (measuring sucrose water vs. water intake), and reserved the final “wall” to attach/detach a running wheel (Figure 2a).…”

Section: Resultsmentioning

confidence: 99%

Clinicopathologic Dissociation: Robust Lafora Body Accumulation in Malin KO Mice Without Observable Changes in Home‐Cage Behavior

Krishnan,

Wu,

Mazumder

et al. 2024

J of Comparative Neurology

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Lafora disease (LD) is a syndrome of progressive myoclonic epilepsy and cumulative neurocognitive deterioration caused by recessively inherited genetic lesions of EPM2A (laforin) or NHLRC1 (malin). Neuropsychiatric symptomatology in LD is thought to be directly downstream of neuronal and astrocytic polyglucosan aggregates, termed Lafora bodies (LBs), which faithfully accumulate in an age‐dependent manner in all mouse models of LD. In this study, we applied home‐cage monitoring to examine the extent of neurobehavioral deterioration in a model of malin‐deficient LD as a means to identify robust preclinical endpoints that may guide the selection of novel genetic treatments. At 6 weeks, ∼6–7 months, and ∼12 months of age, malin‐deficient mice (“KO”) and wild‐type (WT) littermates underwent a standardized home‐cage behavioral assessment designed to non‐obtrusively appraise features of rest/arousal, consumptive behaviors, risk aversion, and voluntary wheel‐running. At all timepoints, and over a range of metrics that we report transparently, WT and KO mice were essentially indistinguishable. In contrast, within WT mice compared across the same timepoints, we identified age‐related nocturnal hypoactivity, diminished sucrose preference, and reduced wheel‐running. Neuropathological examinations in subsets of the same mice revealed expected age‐dependent LB accumulation, gliosis, and microglial activation in cortical and subcortical brain regions. At 12 months of age, despite the burden of neocortical LBs, we did not identify spontaneous seizures during an electroencephalographic (EEG) survey, and KO and WT mice exhibited similar spectral EEG features. However, in an in vitro assay of neocortical function, paroxysmal bursts of network activity (UP states) in KO slices were more prolonged at 3 and 6 months of age, but similar to WT at 12 months. KO mice displayed a distinct response to pentylenetetrazole, with a greater incidence of clonic seizures and a more pronounced postictal suppression of movement, feeding, and drinking behavior. Together, these results highlight the clinicopathologic dissociation in a mouse model of LD, where the accrual of LBs may latently modify cortical circuit function and seizure threshold without clinically meaningful changes in home‐cage behavior. Our findings allude to a delay between LB accumulation and neurobehavioral decline in LD: one that may provide a window for treatment, and whose precise duration may be difficult to ascertain within the typical lifespan of a laboratory mouse.

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Sex-specific cognitive effects of mild traumatic brain injury to the frontal and temporal lobes

Cited by 8 publications

References 46 publications

Four-parameter analysis in modified Rotarod test for detecting minor motor deficits in mice

Four-parameter analysis in modified Rotarod test for detecting minor motor deficits in mice

Sex-specific antioxidant biomarker depletion in patients with a history of mild traumatic brain injury

Clinicopathologic Dissociation: Robust Lafora Body Accumulation in Malin KO Mice Without Observable Changes in Home‐Cage Behavior

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