Serum metalloproteinase 9 levels increase after generalized tonic-clonic seizures

Cudna, Agnieszka; Jopowicz, Anna; Mierzejewski, Paweł; Kurkowska‐Jastrzębska, Iwona

doi:10.1016/j.eplepsyres.2016.11.006

Cited by 23 publications

(20 citation statements)

References 14 publications

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“…Here, the hemisphere ipsilateral to injuries was heavier than the contralateral hemisphere and positively correlated with seizure duration while hemisphere weight was not different between hemispheres in infants. Prolonged seizures cause opening of the blood brain barrier via matrix metalloproteinases ( Goasdoue et al, 2019 ; Dubey et al, 2017 ; Cudna et al, 2017 ). Future studies will aim to determine if development affects the baseline or increase in mediators of blood brain barrier opening.…”

Section: Discussionmentioning

confidence: 99%

A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model

Costine-Bartell

Price

Shen

et al. 2021

Neurobiology of Disease

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The pathophysiology of extensive cortical tissue destruction observed in hemispheric hypodensity, a severe type of brain injury observed in young children, is unknown. Here, we utilize our unique, large animal model of hemispheric hypodensity with multifactorial injuries and insults to understand the pathophysiology of this severe type of traumatic brain injury, testing the effect of different stages of development. Piglets developmentally similar to human infants (1 week old, “infants”) and toddlers (1 month old, “toddlers”) underwent injuries and insults scaled to brain volume: cortical impact, creation of mass effect, placement of a subdural hematoma, seizure induction, apnea, and hypoventilation or a sham injury while anesthetized with a seizure-permissive regimen. Piglets receiving model injuries required overnight intensive care. Hemispheres were evaluated for damage via histopathology. The pattern of damage was related to seizure duration and hemorrhage pattern in “toddlers” resulting in a unilateral hemispheric pattern of damage ipsilateral to the injuries with sparing of the deep brain regions and the contralateral hemisphere. While “infants” had the equivalent duration of seizures as “toddlers”, damage was less than “toddlers”, not correlated to seizure duration, and was bilateral and patchy as is often observed in human infants. Subdural hemorrhage was associate with adjacent focal subarachnoid hemorrhage. The percentage of the hemisphere covered with subarachnoid hemorrhage was positively correlated with damage in both developmental stages. In “infants”, hemorrhage over the cortex was associated with damage to the cortex with sparing of the deep gray matter regions; without hemorrhage, damage was directed to the hippocampus and the cortex was spared. “Infants” had lower neurologic scores than “toddlers”. This multifactorial model of severe brain injury caused unilateral, wide-spread destruction of the cortex in piglets developmentally similar to toddlers where both seizure duration and hemorrhage covering the brain were positively correlated to tissue destruction. Inherent developmental differences may affect how the brain responds to seizure, and thus, affects the extent and pattern of damage. Study into specifically how the “infant” brain is resistant to the effects of seizure is currently underway and may identify potential therapeutic targets that may reduce evolution of tissue damage after severe traumatic brain injury.

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Section: Discussionmentioning

confidence: 99%

A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model

Costine-Bartell

Price

Shen

et al. 2021

Neurobiology of Disease

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“…Over the past decades, the inflammatory and immune responses have been suspected of participating in one of the potential underlying mechanisms for epilepsy (17,18), and intravenous immune globulin has subsequently been used in the treatment of intractable childhood epilepsy. Immune (19)(20)(21)(22), and a relationship has been identified between HLA and epilepsy (23)(24)(25)(26). Furthermore, CXCL1 has an association with epilepsy (27); however, the actual roles of HLA-C and CXCL1 in epilepsy have remained obscure.…”

Section: Discussionmentioning

confidence: 99%

Identification of significant immune-related genes for epilepsy via bioinformatics analysis

Luo¹,

Xiang²,

Huang³

et al. 2021

Ann Transl Med

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Background: Epilepsy is one of the most common neurological disorders, but its underlying mechanism has remained obscure, and the role of immune-related genes (IRGs) in epilepsy have not yet been investigated.Therefore, in this study, we explored the association between IRGs and epilepsy.Methods: An IRG list was collected from the ImmPort database. The gene expression profiles of GSE143272 were collected from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm. nih.gov/geo/). Differentially expressed genes (DEGs) between epilepsy and normal samples were analyzed, and the intersections between IRGs and DEGs were identified using the VennDiagram package, with the intersected genes subjected to further analysis. Enrichment function for intersected genes were performed, constructed a protein-protein interaction (PPI) network via the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the hub genes (top 10) of the PPI network were calculated by the cytoHubba plug-in in Cytoscape. The top correlated genes were selected to perform correlation analysis with immune cells infiltration and expression levels. Finally, we performed validation of the top correlated genes transcriptional expression levels using an animal model.Results: There were a total of 245 DEGs detected in GSE143272, among which 143 were upregulated and 102 downregulated genes in epilepsy. A total of 44 differential IRGs were obtained via intersection of DEGs and IRGs. Enrichment function analysis of DEGs showed that they played a significant role in immune response. The gene CXCL1 was the most correlated with other differentially expressed IRGs via the PPI network. The results of immune cell infiltration analysis indicated that epilepsy patients had higher activated mast cells infiltration (P=0.021), but lower activated CD4 memory T cells (P=0.001), resting CD4 memory T cells (P=0.011), and gamma delta T cells (P=0.038) infiltration. It was revealed that CXCL1 and activated mast cells (R=0.25, P=0.019) and neutrophils (R=0.3, P=0.0043), and a negative correlation with T cells gamma delta (R=−0.25, P=0.018). The levels of CXCL1 expression were significantly lower in epilepsy patients than those in normal samples.Conclusions: In this study, the results showed that IRGs such as CXCL1 have a significant influence on epilepsy via regulation of immune cells infiltration.

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“…In these patients the level of MMP-9 proenzyme and activity in the tissue of epileptic focus was increased in comparison to surrounding tissues and a normal hippocampus [67]. The study performed on with generalized tonic-clonic seizures, patients with convulsive and non-convulsive status epilepticus, and patients with complex partial seizures significant increase of serum MMP-9 in 1 hour and in 24 hours after seizures has been observed, with the return to control level in 72 hours after seizures [70]. In another study cerebrospinal fluid level of MMP-9 in patients with bacterial meningitis who subsequently developed epileptic seizures was higher than in group with no seizure developed [71].…”

Section: Evidence From Clinical Studiesmentioning

confidence: 90%

Metaloproteinaza macierzy pozakomórkowej 9 i epileptogeneza â kluczowa rola enzymu i strategie zmierzające do zapobiegania rozwojowi choroby

Khomiak

Kaczmarek

2018

Postepy Biochem

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Epileptogeneza jest procesem odpowiedzialnym za przemianę zdrowego mózgu w padaczkowy. Ten proces może być spowodowany przez takie zdarzenia, jak uraz mózgu czy stan padaczkowy. Głównym mechanizmem odpowiedzialnym za zmiany mogą być, przede wszystkim, stan zapalny mózgu, zakłócenia ciągłości bariery krew-mózg, patologiczna przebudowa sieci neuronalnych oraz nienaturalna plastyczność synaptyczna. Dane elsperymentalne uzyskane w modelach zwierzęcych oraz u pacjentów z padaczką sugerują, że metaloproteinaza macierzy zewnątrzkomórkowej 9 (MMP-9) jest potencjalnie jednym z kluczowych składników procesu epileptogenezy. MMP-9 wpływa na plastyczność synaptyczną umożliwiając padaczkową reorganizację obwodów neuronalnych w mózgu. Zależne od MMP-9 cięcie elementów bariery krew-mózg i następująca po nim infiltracja komórek układu immunologicznego do mózgu, przyczyniają się do stanu zapalnego w epileptogenezie. Celem danej pracy przeglądowej jest analiza możliwych mechanizmów zaangażowania MMP-9 w proces epileptogenezy oraz koncepcja zahamowania MMP-9 jako potencjalnej strategii terapeutycznej.

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Serum metalloproteinase 9 levels increase after generalized tonic-clonic seizures

Cited by 23 publications

References 14 publications

A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model

A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model

Identification of significant immune-related genes for epilepsy via bioinformatics analysis

Metaloproteinaza macierzy pozakomórkowej 9 i epileptogeneza â kluczowa rola enzymu i strategie zmierzające do zapobiegania rozwojowi choroby

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Serum metalloproteinase 9 levels increase after generalized tonic-clonic seizures

Cited by 23 publications

References 14 publications

A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model

A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model

Identification of significant immune-related genes for epilepsy via bioinformatics analysis

Metaloproteinaza macierzy pozakomórkowej 9 i epileptogeneza â kluczowa rola enzymu i strategie zmierzające do zapobiegania rozwojowi choroby

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Metaloproteinaza macierzy pozakomórkowej 9 i epileptogeneza â kluczowa rola enzymu i strategie zmierzające do zapobiegania rozwojowi choroby