About

Frances Elizabeth Jensen, MD, FACP, FANA, FAAN, FAES, is a Professor of Neurology and Chairman of Neurology at the Perelman School of Medicine, University of Pennsylvania. She is also Co-Director of the Penn Translational Neuroscience Center. Dr. Jensen is a graduate of Cornell Medical College and completed her neurology residency at the Harvard Longwood Neurology Residency Program. Her research focuses on mechanisms of epilepsy and stroke, as well as the mechanistic interaction of epilepsy with other disorders such as autism and dementia, with an emphasis on elucidating new therapies for clinical trials development. She has received notable recognition including the 2007 NIH Director’s Pioneer Award for exploring the interaction between epileptogenesis and cognitive dysfunction and was elected to the National Academy of Medicine in 2015. Dr. Jensen has served as President of the American Epilepsy Society and is currently President-Elect of the American Neurological Association. She has authored over 150 manuscripts related to her research and has been continuously funded by NIH since 1987, including receiving a NIH-NINDS Javits Award in 2020. She has trained numerous clinical and basic research fellows who now hold faculty positions nationally and internationally. Additionally, Dr. Jensen is a Trustee of the Franklin Institute and actively involved in community outreach for brain research and education. She is an advocate for adolescent brain development and is the author of the book 'The Teenage Brain,' published in 2015/16 and translated into over 25 languages.

Research topics

• Medicine
• Neuroscience
• Biology
• Psychology
• Internal medicine

Selected publications

• Posttraumatic Epilepsy and Dementia Risk

  UNC Libraries · 2026-04-21

  articleOpen access

  Importance: Although both head injury and epilepsy are associated with long-term dementia risk, posttraumatic epilepsy (PTE) has only been evaluated in association with short-term cognitive outcomes. Objective: To investigate associations of PTE with dementia risk. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study initially enrolled participants from 1987 to 1989 and this prospective cohort study uses data through December 31, 2019, with a median follow-up of 25 years. Data were analyzed between March 14, 2023, and January 2, 2024. The study took place in 4 US communities in Minnesota, Maryland, North Carolina, and Mississippi. Of 15 792 ARIC study participants initially enrolled, 2061 were ineligible and 1173 were excluded for missing data, resulting in 12 558 included participants. Exposures: Head injury was defined by self-report and International Classification of Diseases (ICD) diagnostic codes. Seizure/epilepsy was defined using ICD codes. PTE was defined as a diagnosis of seizure/epilepsy occurring more than 7 days after head injury. Head injury, seizure/epilepsy, and PTE were analyzed as time-varying exposures. Main Outcomes and Measures: Dementia was defined using cognitive assessments, informant interviews, and ICD and death certificate codes. Adjusted Cox and Fine and Gray proportional hazards models were used to estimate dementia risk. Results: Participants had a mean (SD) age of 54.3 (5.8) years at baseline, 57.7% were female, 28.2% were of self-reported Black race, 14.4% were ultimately categorized as having head injury, 5.1% as having seizure/epilepsy, and 1.2% as having PTE. Over a median follow-up of 25 (25th to 75th percentile, 17-30) years, 19.9% developed dementia. In fully adjusted models, compared with no head injury and no seizure/epilepsy, PTE was associated with 4.56 (95% CI, 4.49-5.95) times the risk of dementia, while seizure/epilepsy was associated with 2.61 (95% CI, 2.21-3.07) times the risk and head injury with 1.63 (95% CI, 1.47-1.80) times the risk. The risk of dementia associated with PTE was significantly higher than the risk associated with head injury alone and with nontraumatic seizure/epilepsy alone. Results were slightly attenuated in models accounting for the competing risks of mortality and stroke, but patterns of association remained similar. In secondary analyses, the increased dementia risk associated with PTE occurring after first vs second head injury and after mild vs moderate/severe injury was similar. Conclusions and Relevance: In this community-based cohort, there was an increased risk of dementia associated with PTE that was significantly higher than the risk associated with head injury or seizure/epilepsy alone. These findings provide evidence that PTE is associated with long-term outcomes and supports both the prevention of head injuries via public health measures and further research into the underlying mechanisms and the risk factors for the development of PTE, so that efforts can also be focused on the prevention of PTE after a head injury.

  PublisherDOI

• Amplifying and ameliorating light avoidance in mice with photoreceptor targeting and CGRP sensitization

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-28

  preprintOpen accessSenior author

  Abstract Objective To determine the photoreceptor basis of light avoidance in mice and assess the effect of CGRP sensitization on this behavior. Background Prior studies have suggested that photophobia is mediated by a subset of retinal ganglion cells (RGCs) that contain melanopsin, making them intrinsically photosensitive (ipRGCs). These cells also receive extrinsic input from cones, which can also mediate light sensitivity. Here, we examined whether spectral variation targeting melanopsin or specific cone types in mice could effectively model light sensitivity. Also, we assessed whether sensitizing mice with calcitonin gene-related peptide (CGRP) could amplify ipRGC-mediated light avoidance. Methods Light avoidance behavior was observed in a two-zone chamber illuminated by narrow-band LEDs targeting photopic opsins: 365 nm (UV; rodent S-cone), 460 nm (blue; melanopsin), and 630 nm (red; human L-cone). In a non-targeted assay, we assessed the degree of light avoidance in wildtype C57BL/6J mice to varying intensities (5 to 100%) of the blue and red LEDs. In a targeted assay, mice were given a choice to spend time between zones with differing relative contrast levels (0.50, 0.75, or 1.00) for the targeted photoreceptor(s). This was assessed in two transgenic mice with: 1) human red cone knock-in (RCKI), or 2) adult-onset ablation of M1 ipRGCs ( Opn4 aDTA ). Mice were studied without intervention or following priming with either peripheral CGRP or vehicle administration every other day for 9 days. A primary measure (mean +/- SEM) was the asymptote value (AV). Results Wildtype mice showed greater light avoidance with increasing light intensity, demonstrating a parametric response. RCKI mice showed avoidance of the high melanopsin (1.00: 0.52 ± 0.08; n = 18) and L-cone (1.00: 0.30 ± 0.11; n = 15) contrast zones but showed a preference for the higher S-cone (1.00: −0.35 ± 0.06; n = 16) contrast zone. These effects decreased with less relative contrast and, thus, contrast dependent. Adding S-cone contrast opposed avoidance to melanopsin (0.10 ± 0.12; n = 14) or L-cone (−0.19 ± 0.10; n = 15) contrast. Ablation of ipRGCs in Opn4 aDTA mice attenuated avoidance of melanopsin and preference for S-cone stimulation compared to control littermates. On day 9, CGRP priming led to significantly increased avoidance of melanopsin stimulation (0.58 ± 0.08, n = 21) as compared to vehicle priming (0.26 ± 0.09, n = 22) ( F (1,41) = 5.70, p = 0.02). Conclusions Our findings further support that ipRGCs play a key role in mediating photophobia. This aversive response to light stems from ipRGCs combining excitatory input from intrinsic melanopsin stimulation and extrinsic L-cone input, which can be opposed by extrinsic inhibitory S-cone input. Chronic exposure to CGRP is likely one of many mechanisms in migraine that can amplify ipRGC signals, leading to photophobia. Plain Language Summary To better understand light sensitivity, we studied which cells in the eye cause mice to avoid light. We found that mice avoided blue and red light but preferred UV light, and this is the result of a special cell (ipRGCs) in the eye that combines these light signals. Repeated exposure to CGRP, a key nervous system messenger in migraine, increased avoidance of blue light, which may model what happens in people with chronic migraine who experience light sensitivity.

  PublisherOA PDFDOI

• Amplifying and ameliorating light avoidance in mice with photoreceptor targeting and calcitonin gene‐related peptide sensitization

  Headache The Journal of Head and Face Pain · 2025-12-15

  articleOpen accessSenior author

  Abstract Objective The aim of this study was to determine the photoreceptor basis of light avoidance in mice and assess the effect of CGRP sensitization on this behavior. Background Prior studies have suggested that photophobia is mediated by a subset of retinal ganglion cells (RGCs) that contain melanopsin, making them intrinsically photosensitive (ipRGCs). These cells also receive extrinsic input from cones, which can also mediate light sensitivity. Here, we examined how spectral targeting of melanopsin or specific cone types in mice produces light avoidance and whether sensitizing mice with calcitonin gene‐related peptide (CGRP) amplifies the avoidance response to ipRGC stimulation. Methods Light avoidance behavior was measured in a two‐zone chamber illuminated by narrow‐band light‐emitting diodes (LEDs) targeting photopic opsins: 365 nm (ultraviolet [UV]; rodent S‐cone), 460 nm (blue; melanopsin), and 630 nm (red; human L‐cone). In a non‐targeted assay, we assessed the degree of light avoidance in wild‐type (WT) C57BL/6J mice to varying contrasts (0.05 to 1.00) of the blue and red LEDs. In a targeted assay, mice were exposed to zones with differing relative contrast levels (0.50, 0.75, or 1.00) for the targeted photoreceptor(s). This was assessed in transgenic mice with: (1) human L‐cone cone knock‐in (HLCKI) or (2) adult‐onset ablation of M1 ipRGCs (Opn4 aDTA ). Mice were studied without intervention or following chronic intermittent administration of CGRP with either peripheral CGRP or vehicle (Veh) administration every‐other‐day for 9 days. A primary measure (mean +/− SEM) was the asymptote value (AV) of chamber preference. Results WT mice showed greater light avoidance with increasing light contrast. HLCKI mice avoided zones with high melanopsin (1.00: 0.52 ± 0.08; n = 18) and L‐cone (1.00: 0.30 ± 0.11; n = 15) stimulation but showed a preference for the zone with higher S‐cone (1.00: −0.35 ± 0.06; n = 16) stimulation. These effects were contrast‐dependent. The addition of S‐cone stimulation reduced the aversive effect of melanopsin (0.10 ± 0.12; n = 14) or L‐cone (−0.19 ± 0.10; n = 15) contrast. Ablation of ipRGCs in HLCKI x Opn4 aDT A mice eliminated both avoidance of melanopsin stimulation and the preference for S‐cone stimulation, as compared to controls. Nine days of chronic intermittent administration of CGRP led to significantly increased avoidance of melanopsin stimulation (0.58 ± 0.08, n = 21) as compared to Veh administration (0.26 ± 0.09, n = 22) ( F (1, 41) = 5.70, p = 0.022). Conclusions Our findings support a key role for the ipRGCs in the production of photophobia. This aversive response to light stems from integrated ipRGC signals that combine excitatory intrinsic melanopsin and extrinsic L‐cone inputs and are opposed by extrinsic, inhibitory S‐cone input. Chronic elevation of CGRP levels in migraine may amplify ipRGC signals, leading to photophobia.

  PublisherDOI

• Temporal and cell-specific changes to cellular iron sequestration and lipid peroxidation in a murine model of neonatal hypoxic-ischemic brain injury

  Neurobiology of Disease · 2025-07-03

  preprintOpen access

  Abstract Background Iron accumulation and lipid peroxidation are pathophysiologic mechanisms that drive neonatal hypoxic-ischemic (HI) brain injury. Characterization of spatiotemporal changes in these processes will help elucidate their role in ischemic neuronal injury as an initial step towards developing targeted interventions. Methods HI was induced in post-natal day 9 mice using the modified-Vannucci model. Hippocampal tissue from ipsilateral HI exposed, contralateral hypoxia exposed and sham animals was collected at 6h, 24h, 72h and 7d post-HI. Tissue was subsequently evaluated for markers of cell death (TUNEL), intracellular iron changes (FerroOrange, fluorescent in situ and immunofluorescence), and lipid peroxidation (real time PCR, Gpx4 immunofluorescence and mass spectrometry). Mass spectrometry measured isoprostanes (15-F 2t -IsoP) and neuroprostanes (4-F 4t -NP) as lipid peroxidation markers of arachidonic (ARA) and docosahexaenoic acid (DHA), respectively. Results Compared to sham, the HI hippocampus showed increased intracellular labile iron levels that was maximal at 6h post-HI with subsequent elevation in only neuroprostanes at 24h post-HI. TUNEL labeling peaked at 24h post-HI. At 72h, labile iron levels and lipid peroxidation declined corresponding with peak infiltration of ferritin positive microglia/macrophages and the start of TUNEL staining decline. In addition, surviving neurons had increased expression of Gpx4 peaking at 72h post-HI that normalized by 7d post-HI. Conclusions These findings suggest that following HI, an acute increase in labile iron and DHA peroxidation are correlated with markers of cell death that peak at 24h post-HI. Microglial/macrophage iron sequestration and neuronal antioxidant responses may ameliorate further injury and represent targets for neuroprotective therapies.

  PublisherDOI

• S-cone Stimulation Opposes Aversion to Melanopsin and L-cone Stimulation in a Preclinical Model of Photophobia (S20.002)

  Neurology · 2024-04-09

  articleSenior author

  To measure avoidance to stimuli targeting melanopsin, L-cones, and/or S-cones in a mouse model of migraine.

  PublisherDOI

• Seizure‐activated neurons facilitate tau spread in 5XFAD mice

  Alzheimer s & Dementia · 2024-12-01

  articleOpen accessSenior author

  BACKGROUND: Seizures are highly comorbid with Alzheimer's disease (AD). We and others have demonstrated worsened pathological and cognitive outcomes in AD patients with seizure history and after seizure induction in AD mouse models. Central to AD progression is the spread of tau along neuronal connections, which can be modelled by intracerebral injection of human AD brain derived tau lysate (AD-tau), but whether seizures impact the spread of tau is unknown. We hypothesized that seizures would worsen tau spread and that neurons activated during seizures would have increased susceptibility to develop and possibly transmit tau pathology. METHODS: To investigate seizure-tau interactions, we crossed the 5XFAD mouse model with targeted recombination in active populations mice (TRAP; 5X-/WT-TRAP) to permanently label seizure-activated neurons. We injected AD-tau unilaterally into the hippocampus and overlying cortex (1 µg/site) at three months of age in 5X-TRAP and WT-TRAP littermates. Seizures were then induced with pentylenetetrazol (PTZ) kindling 2-3 weeks following surgery and seizure-activated neurons were induced to express tdTomato on the final day of kindling via 4-hydroxytamoxifen administration. Three months following AD-tau seeding, 5X-/WT-TRAP brains were serially sectioned and underwent immunofluorescent slide scanning. Scanned brain images were then registered to the Allen Brain Atlas and mapped for seizure-activated neurons (tdTomato+) and tau pathology (phospho-tau Ser202/Ser205; AT8). RESULTS: We found that 5X-TRAP mice had increased tau pathology compared to WT-TRAP in hippocampal subregions ipsilateral to AD-tau injection, including the dentate gyrus (p<0.05, n = 5-10/group) and subiculum (p<0.01, n = 5-9/group), regardless of seizure kindling, without changes in the contralateral hippocampus. Seizure induction resulted in increased tau spread in remote interconnected brain regions, including the ipsilateral and contralateral thalamo-cortical regions (p<0.05, n = 5-9/group). In addition, we found that, compared to neurons from a saline-treated 5XFAD mouse, thalamic seizure-activated (tdTomato+) neurons showed significantly increased somatic AT8 levels (p<0.05, n = 8-11), while surrounding (tdTomato-) neurons from 5XFAD mice did not, suggesting that these thalamic, seizure-activated neurons preferentially facilitate tau spread. CONCLUSION: Together, our data demonstrate that seizures increase tau spread in mouse models and identify seizures and seizure-activated neurons as therapeutic targets to slow pathological AD progression.

  PublisherOA PDFDOI

• Hyperactive neuronal networks enhance tau spread in an Alzheimer’s disease mouse model

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-02 · 7 citations

  preprintOpen accessSenior authorCorresponding

  Pathological tau spreads via neuronal connections in Alzheimer's disease (AD). Given the high incidence and deleterious consequences of epileptiform activity in AD, we hypothesized that neuronal hyperactivity and seizures exacerbate tau spread. To examine the impacts of brain-wide network and population hyperactivity on tau spread, we created a novel mouse model involving the cross of targeted recombination in active populations (TRAP) and the 5 times familial AD mice (5X-TRAP) that allows for the permanent labelling of seizure-activated neurons. To explore the effects of seizures on tau spread, we injected these mice with human AD brain-derived tau to induce pathological tau spread, and induced seizures with pentylenetetrazol (PTZ) kindling. Brain mapping revealed that seizures increased tau spread in 5X-TRAP mice, which correlated extensively with memory deficits in PTZ kindled 5X-TRAP mice. Using computational models, we found data supportive of increased anterograde tau spread in 5X-TRAP mice and that regional neuronal activity levels were predictive of tau pathology. On a cellular level, we found that hyperactive neurons drive elevated tau propagation in 5X-TRAP mice. We also found corroborating evidence of increased tau spread in AD patients with a seizure history compared to those without. Our study identifies neuronal hyperactivity and seizures as key, targetable factors underlying AD progression.

  PublisherOA PDFDOI

• Cannabidiol attenuates seizure susceptibility and behavioural deficits in adult CDKL5 ^R59X knock‐in mice

  European Journal of Neuroscience · 2024-04-23 · 10 citations

  articleOpen accessSenior authorCorresponding

  Abstract Cyclin‐dependent kinase‐like 5 (CDKL5) deficiency disorder (CDD) is caused by a loss‐of‐function mutation in CDKL5 gene, encoding a serine–threonine kinase highly expressed in the brain. CDD manifests with early‐onset epilepsy, autism, motor impairment and severe intellectual disability. While there are no known treatments for CDD, the use of cannabidiol has recently been introduced into clinical practice for neurodevelopmental disorders. Given the increased clinical utilization of cannabidiol, we examined its efficacy in the CDKL5 R59X knock‐in (R59X) mice, a CDD model based on a human mutation that exhibits both lifelong seizure susceptibility and behavioural deficits. We found that cannabidiol pre‐treatment rescued the increased seizure susceptibility in response to the chemoconvulsant pentylenetetrazol (PTZ), attenuated working memory and long‐term memory impairments, and rescued social deficits in adult R59X mice. To elucidate a potential mechanism, we compared the developmental hippocampal and cortical expression of common endocannabinoid (eCB) targets in R59X mice and their wild‐type littermates, including cannabinoid type 1 receptor (CB1R), transient receptor potential vanilloid type 1 (TRPV1) and 2 (TRPV2), G‐coupled protein receptor 55 (GPR55) and adenosine receptor 1 (A1R). Many of these eCB targets were developmentally regulated in both R59X and wild‐type mice. In addition, adult R59X mice demonstrated significantly decreased expression of CB1R and TRPV1 in the hippocampus, and TRPV2 in the cortex, while TRPV1 was increased in the cortex. These findings support the potential for dysregulation of eCB signalling as a plausible mechanism and therapeutic target in CDD, given the efficacy of cannabidiol to attenuate hyperexcitability and behavioural deficits in this disorder.

  PublisherOA PDFDOI

• Contributors

  Elsevier eBooks · 2024-10-16

  book-chapterOpen access
  PublisherDOI

• Posttraumatic Epilepsy and Dementia Risk

  JAMA Neurology · 2024-02-26 · 12 citations

  articleOpen access

  Importance: Although both head injury and epilepsy are associated with long-term dementia risk, posttraumatic epilepsy (PTE) has only been evaluated in association with short-term cognitive outcomes. Objective: To investigate associations of PTE with dementia risk. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study initially enrolled participants from 1987 to 1989 and this prospective cohort study uses data through December 31, 2019, with a median follow-up of 25 years. Data were analyzed between March 14, 2023, and January 2, 2024. The study took place in 4 US communities in Minnesota, Maryland, North Carolina, and Mississippi. Of 15 792 ARIC study participants initially enrolled, 2061 were ineligible and 1173 were excluded for missing data, resulting in 12 558 included participants. Exposures: Head injury was defined by self-report and International Classification of Diseases (ICD) diagnostic codes. Seizure/epilepsy was defined using ICD codes. PTE was defined as a diagnosis of seizure/epilepsy occurring more than 7 days after head injury. Head injury, seizure/epilepsy, and PTE were analyzed as time-varying exposures. Main Outcomes and Measures: Dementia was defined using cognitive assessments, informant interviews, and ICD and death certificate codes. Adjusted Cox and Fine and Gray proportional hazards models were used to estimate dementia risk. Results: Participants had a mean (SD) age of 54.3 (5.8) years at baseline, 57.7% were female, 28.2% were of self-reported Black race, 14.4% were ultimately categorized as having head injury, 5.1% as having seizure/epilepsy, and 1.2% as having PTE. Over a median follow-up of 25 (25th to 75th percentile, 17-30) years, 19.9% developed dementia. In fully adjusted models, compared with no head injury and no seizure/epilepsy, PTE was associated with 4.56 (95% CI, 4.49-5.95) times the risk of dementia, while seizure/epilepsy was associated with 2.61 (95% CI, 2.21-3.07) times the risk and head injury with 1.63 (95% CI, 1.47-1.80) times the risk. The risk of dementia associated with PTE was significantly higher than the risk associated with head injury alone and with nontraumatic seizure/epilepsy alone. Results were slightly attenuated in models accounting for the competing risks of mortality and stroke, but patterns of association remained similar. In secondary analyses, the increased dementia risk associated with PTE occurring after first vs second head injury and after mild vs moderate/severe injury was similar. Conclusions and Relevance: In this community-based cohort, there was an increased risk of dementia associated with PTE that was significantly higher than the risk associated with head injury or seizure/epilepsy alone. These findings provide evidence that PTE is associated with long-term outcomes and supports both the prevention of head injuries via public health measures and further research into the underlying mechanisms and the risk factors for the development of PTE, so that efforts can also be focused on the prevention of PTE after a head injury.

  PublisherOA PDFDOI

Recent grants

• NIH Grant P01NS038475

  NIH · $26.1M · 2010

• Early Life Seizures Disrupt Critical Period Plasticity

  NIH · $1.8M · 2013–2018

• NIH Grant R21NS080268

  NIH · $438k · 2015

• Tracking the evolution of synaptic dysplasticity after early life seizures

  NIH · $3.4M · 2024–2027

• NIH Grant RC1NS068938

  NIH · $814k · 2012

Frequent coauthors

• Joseph J. Volpe

  70 shared

• Delia M. Talos

  California University of Pennsylvania

  64 shared

• Paul A. Rosenberg

  Harvard University

  58 shared

• Solomon L. Moshé

  Montefiore Medical Center

  41 shared

• Ésper A. Cavalheiro

  Universidade Federal de São Paulo

  38 shared

• Maria da Graça Naffah‐Mazzacoratti

  Universidade Federal de São Paulo

  37 shared

• Dennis Päsler

  Universität Greifswald

  36 shared

• K Jandová

  Charles University

  36 shared

Labs

• Jensen LabPI

Awards & honors

• 2007 Director’s Pioneer Award from the NIH
• Elected as a member of the National Academy of Medicine (201…
• President of the American Epilepsy Society (2012)
• NIH-NINDS Javits Award (2020)
• Trustee of the Franklin Institute in Philadelphia