Regular ArticleProgesterone Facilitates Cognitive Recovery and Reduces Secondary Neuronal Loss Caused by Cortical Contusion Injury in Male Rats
Abstract
The ability of progesterone to reduce the cerebral edema associated with traumatic brain damage first became apparent when we observed that males had significantly more edema than females after cortical contusion. In addition, edema was almost absent in pseudopregnant female rats, a condition in which progesterone levels are high relative to estrogen. Progesterone injections given after injury also reduced edema and were equally effective in both males and females. The present experiment was done to determine if the progesterone-induced reduction in edema could also prevent secondary neuronal degeneration and reduce the behavioral impairments that accompany contusion of the medial frontal cortex. Progesterone-treated rats were less impaired on a Morris water maze spatial navigation task than rats treated with the oil vehicle. Progesterone-treated rats also showed less neuronal degeneration 21 days after injury in the medial dorsal thalamic nucleus, a structure that has reciprocal connections with the contused area.
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Head Injury and Pregnancy—Does the Outcome Differ? A Descriptive Analysis of 15 Years from a Single Tertiary Care Center
2022, World NeurosurgeryThere are conflicting data about the outcome of head injury in pregnant patients. Since they comprise a small proportion of the traumatic brain−injured (TBI) patients, the literature is sparse on true evidence on this issue.
A 15-year observational study to analyze the outcome of TBI in pregnant women admitted to a level 1 trauma center from 2005−2020 was carried out with the approval of institutional review board. Female patients aged 18−50 years admitted with TBI were included. Patients with polytrauma or dead-on arrival to the emergency department were excluded from the study. The vital parameters, Glasgow Coma Scale (GCS) score at admission, Rotterdam computed tomography (CT) scan, severity score, and Glasgow Outcome Score (GOS) at 3 months were collected from the trauma database, discharge summaries, and patient records.
During the study period, 5071 patients with head injury were admitted. Among the 228 patients who met inclusion criteria, 31 (13.6%) were pregnant with a mean age of 24.2 ± 3.8 years. The Rotterdam CT severity score, which moderately correlated with outcome in the control group, was found to be a poor predictor in the pregnant group. The outcome measures were compared using GCS score at discharge for immediate and GOS at 3 months for long-term periods. A better functional outcome was observed at 3 months among pregnant patients (P = 0.02).
Pregnant TBI patients have better long-term outcomes than their similar-aged counterparts. However, radiologic severity of injury does not seem to predict outcome in this cohort.
Antioxidant therapies in traumatic brain injury
2022, Neurochemistry InternationalOxidative stress plays a crucial role in traumatic brain injury (TBI) pathogenesis. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) formed in excess after TBI synergistically contribute to secondary brain damage together with lipid peroxidation products (reactive aldehydes) and inflammatory mediators. Furthermore, oxidative stress, endoplasmic reticulum stress and inflammation potentiate each other. Following TBI, excessive oxidative stress overloads the endogenous cellular antioxidant system leading to cell death. To combat oxidative stress, several antioxidant therapies were tested in preclinical animal models of TBI. These include free radical scavengers, activators of antioxidant systems, Inhibitors of free radical generating enzymes and antioxidant enzymes. Many of these therapies showed promising outcomes including reduced edema, blood-brain barrier (BBB) protection, smaller contusion volume, and less inflammation. In addition, many antioxidant therapies also promoted better sensory, motor, and cognitive functional recovery after TBI. Overall, preventing oxidative stress is a viable therapeutic option to minimize the secondary damage and to improve the quality of life after TBI.
Progesterone treatment following traumatic brain injury in the 11-day-old rat attenuates cognitive deficits and neuronal hyperexcitability in adolescence
2020, Experimental NeurologyTraumatic brain injury (TBI) in children younger than 4 years old results in cognitive and psychosocial deficits in adolescence and adulthood. At 4 weeks following closed head injury on postnatal day 11, male and female rats exhibited impairment in novel object recognition memory (NOR) along with an increase in open arm time in the elevated plus maze (EPM), suggestive of risk-taking behaviors. This was accompanied by an increase in intrinsic excitability and frequency of spontaneous excitatory post-synaptic currents (EPSCs), and a decrease in the frequency of spontaneous inhibitory post-synaptic currents in layer 2/3 neurons within the medial prefrontal cortex (PFC), a region that is implicated in both object recognition and risk-taking behaviors. Treatment with progesterone for the first week after brain injury improved NOR memory at the 4-week time point in both sham and brain-injured rats and additionally attenuated the injury-induced increase in the excitability of neurons and the frequency of spontaneous EPSCs. The effect of progesterone on cellular excitability changes after injury may be related to its ability to decrease the mRNA expression of the β3 subunit of the voltage-gated sodium channel and increase the expression of the neuronal excitatory amino acid transporter 3 in the medial PFC in sham- and brain-injured animals and also increase glutamic acid decarboxylase mRNA expression in sham- but not brain-injured animals. Progesterone treatment did not affect injury-induced changes in the EPM test. These results demonstrate that administration of progesterone immediately after TBI in 11-day-old rats reduces cognitive deficits in adolescence, which may be mediated by progesterone-mediated regulation of excitatory signaling mechanisms within the medial PFC.
Acute progesterone injection has been shown to reduce brain edema following traumatic brain injury (TBI) due to its neuroprotective effect. We investigated the effects of sustained release of progesterone through implantation of subcutaneous capsules on rat's brain edema and alteration of cerebrospinal fluid (CSF), and serum ratio of NGF/IL-6 after TBI. This experiment was performed on ovariectomized (OVX) rats and the brain injury was induced by Marmarou's method. A high and a low dose of progesterone (HP and LP) was injected intraperitoneally two h after the brain injury. In addition, in the capsule progesterone-treated group (CP), the intervention was implemented 6 h after the brain injury. Brain edema, NGF and IL-6 biomarkers in serum and cerebrospinal fluid (CSF) were measured 48 h after the TBI in injection groups and one week after the TBI in the CP group. No significant difference was found in the two groups or in the admonition methods. After TBI, the NGF level increased and IL-6 level decreased by injection of both doses, as well as by taking the capsule. Ratio of NGF/IL-6 in CSF increased significantly by all forms of progesterone administration. The increase in the level of NGF and IL-6 after TBI was higher in CSF than in serum. These results indicated that effects of progesterone in capsule form were better than the injection form. Progesterone probably works by increasing NGF and reducing IL-6. Future studies should investigate the ratio of these biomarkers as a variable to determine the neuroprotective effects of another drug.
Neuroprotection in the injured spinal cord
2020, Handbook of Innovations in Central Nervous System Regenerative MedicineSpinal cord injury (SCI) is a devastating and traumatic condition that affects motor, sensory, and autonomic systems. SCI also represents a major economic burden to society without any effective therapeutic treatment available. Current management only relies on the stabilization and acute surgical decompression of the spinal cord and, in some cases, the administration of the antiinflammatory methylprednisolone. However, some controversy in safety and dosage administration remains associated with this drug. Therefore, there is a need to develop and translate novel pharmacological strategies that can promote neuroprotection of the spinal cord with clinical relevance. Acute SCI is a complex and dynamic set of secondary events such as vascular disruption, ionic imbalance, excitotoxicity, and exacerbated inflammatory responses. Preclinical therapies have been developed aiming to promote neuroprotection of the damaged neuronal circuities. This chapter will focus on new neuroprotective therapies employed in the acute phase of the SCI.
Traumatic brain injury in pregnancy
2020, Handbook of Clinical NeurologyTrauma is the leading cause of nonobstetric maternal mortality and affects up to 8% of all pregnancies. Pregnant patients with traumatic brain injury (TBI) are an especially vulnerable population, and their management is complex, with multiple special considerations that must be taken into account. These include but are not limited to alterations in maternal physiology that occur with pregnancy, potential teratogenicity of pharmacologic therapies and diagnostic studies using ionizing radiation, need for fetal monitoring, Rh immunization status, placental abruption, and preterm labor. Despite these challenges, evidence regarding management of the pregnant patient with a TBI is lacking, limited to only case reports/series and retrospective analyses. Despite this uncertainty, expert opinion on management of these patients seems to be that, overall, the standard therapies for management of TBI are safe and effective in pregnancy, with a few notable exceptions described in this chapter. Significant work is needed to continue to develop best-practice and evidence-based guidelines for the management of TBI pregnancy.