Novel rodent models of penetrating traumatic brain injury

A penetrating traumatic brain injury（pTBI）occurs when an object impacts the head with sufficient energy to penetrate skin,cranial bone and meninges to inflict injury directly to the brain parenchyma.This type of injury is particularly common in areas plagued by armed conflicts or gun-related violence.

Transorbital nonmissile penetrating brain injury: Report of two cases

BACKGROUND Penetrating brain injury(PBI) is an uncommon emergency in neurosurgery, and transorbital PBI is a rare type of PBI. Reasonable surgical planning and careful postoperative management can improve the prognosis of patients CASE SUMMARY The first case is a 68-year-old male patient who was admitted to the hospital because a branch punctured his brain through the orbit for approximately 9 h after he unexpectedly fell while walking. After admission, the patient underwent emergency surgical treatment and postoperative anti-infection treatment. The patient was able to follow instructions at a 4-mo follow-up review. The other case is a 46-year-old male patient who was admitted to the hospital due to an intraorbital foreign body caused by a car accident, after which the patient was unconscious for approximately 6 h. After admission, the patient underwent emergency surgical treatment and postoperative anti-infection treatment. The patient could correctly answer questions at a 3-mo follow-up review.CONCLUSION Transorbital PBI is a rare and acute disease. Early diagnosis, surgical intervention, and application of intravenous antibiotics can improve the prognosis and quality of life of patients.

Simultaneous determination of LY3214996,abemaciclib,and M2 and M20 metabolites in human plasma,cerebrospinal fluid,and brain tumor by LC-MS/MS

A sensitive and rapid liquid chromatography tandem mass spectrometry(LC-MS/MS)method was established for the quantification of total and unbound concentrations of LY3214996,an extracellular signal-regulated kinase inhibitor;abemaciclib,a cyclin-dependent kinase 4/6 inhibitor;and abemaciclib active metabolites,M2 and M20,in human plasma,brain tumor,and cerebrospinal fluid samples.The method was validated over a concentration range of 0.2e500 nM within a total run time of 3.8 min using isocratic elution on a Kinetex^(TM) F_(5) column.Detection was performed on a Sciex QTRAP 6500t mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization.The intra-and inter-batch accuracy as well as the precision of the method for all matrices was within ±20% and ≤20% at the lower limit of quantification,and within ±15% and ≤15% for other quality control levels for all analytes.The unbound fractions of drugs and metabolites in spiked and patient samples were determined using an optimized equilibrium dialysis.The validated method was successfully applied in a phase 0/2 clinical trial to assess the central nervous system penetration of LY3214996 and abemaciclib.

Unraveling the drug distribution in brain enabled by MALDI MS imaging with laser-assisted chemical transfer

Accurate localization of central nervous system(CNS)drug distribution in the brain is quite challenging to matrix-assisted laser desorption/ionization(MALDI)mass spectrometry imaging(MSI),owing to the ionization competition/suppression of highly abundant endogenous biomolecules and MALDI matrix.Herein,we developed a highly efficient sample preparation technique,laser-assisted chemical transfer(LACT),to enhance the detection sensitivity of CNS drugs in brain tissues.A focused diode laser source transilluminated the tissue slide coated with α-cyano-4-hydroxycinnamic acid,an optimal matrix to highly absorb the laser radiation at 405 nm,and a very thin-layer chemical film mainly containing drug molecule was transferred to the acceptor glass slide.Subsequently,MALDI MSI was performed on the chemical film without additional sample treatment.One major advantage of LACT is to minimize ionization competition/suppression from the tissue itself by removing abundant endogenous lipid and protein components.The superior performance of LACT led to the successful visualization of regional distribution patterns of 16 CNS drugs in the mouse brain.Furthermore,the dynamic spatial changes of risperidone and its metabolite were visualized over a 24-h period.Also,the brain-to-plasma(B/P)ratio could be obtained according to MALDI MSI results,providing an alternative means to assess brain penetration in drug discovery.

Curcumin-loaded polymeric nanoparticles for neuro-protection in neonatal rats with hypoxic-ischemic encephalopathy

Hypoxic-ischemic encephalopathy is the leading cause of permanent brain injury in term newborns and currently has no cure. Inflammatory processes play a key role in the progression of this disease and may be amenable to a targeted pharmaceutical intervention. Curcumin is a dietary compound with potent anti-inflammatory, antioxidant, and antiapoptotic properties but is limited in therapeutic applications due to its low aqueous solubility, low bioavailability, and rapid first-pass hepatic metabolism. To address these limitations, loading curcumin into poly（lactic-co-glycolic acid）-poly（ethylene glycol） （PLGA-PEG） nanoparticles may increase relevant pharmacokinetic parameters and allow for effective drug delivery to the brain. Using the Vannucci model of unilateral hypoxic-ischemic brain injury in neonatal rats, we studied the in vivo effect of curcumin-loaded PLGA-PEG nanoparticles on brain uptake and diffusion of curcumin and on neuroprotection. The curcumin-loaded nanoparticles were able to overcome the impaired blood-brain barrier, diffuse effectively through the brain parenchyma, localize in regions of injury, and deliver a protective effect in the injured neonatal brain. The application of curcumin and PLGA-PEG nanoparticle-mediated delivery to a clinically relevant model of neonatal brain injury provides greater opportunities for clinical translation of targeted therapies for hypoxic-ischemic encephalopathy.

Civilian gunshot wounds to the head:a case report,clinical management,and literature review

Background:Civilian gunshot wounds to the head refer to brain injury caused by projectiles such as gun projectiles and various fragments generated by explosives in a power launch or explosion.Gunshot wounds to the head are the deadliest of all gun injuries.According to literature statistics,the survival rate of patients with gunshot wounds to the head is only 9%.Due to the strict management of various types of firearms,they rarely occur,so the injury mechanism,injury and trauma analysis,clinical management,and surgical standards are almost entirely based on military experience,and there are few related reports,especially of the head,in which an individual suffered a fatal blow more than once in a short time.We report a case with a return to almost complete recovery despite the patient suffering two gunshot injuries to the head in a short period of time.Case presentations:We present a case of a 53-year-old man who suffered two gunshot injuries to the head under unknown circumstances.On initial presentation,the patient had a Glasgow Coma Scale score of 6,was unable to communicate,and had loss of consciousness.The first bullet penetrated the right frontal area and finally reached the right occipital lobe.When the patient reflexively shielded his head with his hand,the second bullet passed through the patient’s right palm bone,entered the right frontotemporal area,and came to rest deep in the lateral sulcus.The patient had a cerebral hernia when he was admitted to the hospital and immediately entered the operating room for rescue after a computed tomography scan.After two foreign body removals and skull repair,the patient recovered completely.Conclusions:Gunshot wounds to the head have a high mortality rate and usually require aggressive management.Evaluation of most gunshot injuries requires extremely fast imaging examination upon arrival at the hospital,followed by proactive treatment against infection,seizure,and increased intracranial pressure.Surgical intervention is usually necessary,and its key points include the timing,method,and scope of the operation.